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St. John’s Wort Modulates the Toxicities and Pharmacokinetics of CPT-11 (Irinotecan) in Rats

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CPT-11 is a DNA topoisomerase I inhibitor for the therapy of colorectal cancer, whereas St. John’s Wort (Hypericum perforatum, SJW) is a widely used herbal anti-depressant. This study aimed to investigate the effects of co-administered SJW on the toxicities and pharmacokinetics of CPT-11 and the underlying mechanisms. The body weight loss, gastrointestinal and hematological toxicities induced by CPT-11, and the pharmacokinetic parameters of CPT-11 were evaluated in rats pretreated with SJW or vehicle. Rats treated with CPT-11 alone experienced rapid decrease in body weight, whereas co-administration of SJW with CPT-11 resulted in lesser body weight loss. The gastrointestinal and hematological toxicities following CPT-11 injection were both alleviated in the presence of SJW. The rat pharmacokinetics of both CPT-11 and its metabolite SN-38 were significantly altered in presence of SJW. In conclusion, co-administered SJW significantly ameliorated the toxicities induced by CPT-11. The protective effect of SJW may be partially due to pharmacokinetic interaction between CPT-11 and SJW.

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Abbreviations

CPT-11:

rinotecan

DMSO:

dimethylsulfoxide

LOQ:

limit of quantification

SJW:

St. John’s wort

SN-38G:

SN-38 glucuronide

Topo:

topoisomerase

References

  1. M. R. Redinbo L. Stewart P. Kuhn J. J. Champoux W. G. Hol (1998) ArticleTitleCrystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA Science 279 1504–1513 Occurrence Handle10.1126/science.279.5356.1504 Occurrence Handle1:CAS:528:DyaK1cXhs1Kntro%3D Occurrence Handle9488644

    Article  CAS  PubMed  Google Scholar 

  2. L. Stewart M. R. Redinbo X. Qiu W. Hol J. J. Champoux (1998) ArticleTitleA model for the mechanism of human topoisomerase I Science 279 1534–1541 Occurrence Handle1:CAS:528:DyaK1cXhs1Kmurk%3D Occurrence Handle9488652

    CAS  PubMed  Google Scholar 

  3. F. Goldwasser T. Shimizu J. Jackman Y. Hoki P. M. O’Connor K. W. Kohn Y. Pommier (1996) ArticleTitleCorrelations between S and G2 arrest and the cytotoxicity of camptothecin in human colon carcinoma cells Cancer Res. 56 4430–4437 Occurrence Handle1:CAS:528:DyaK28XmtVyltLw%3D Occurrence Handle8813137

    CAS  PubMed  Google Scholar 

  4. T. Kunimoto K. Nitta T. Tanaka N. Uehara H. Baba M. Takeuchi T. Yokokura S. Sawada T. Miyasaka M. Mutai (1987) ArticleTitleAntitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors Cancer Res. 47 5944–5947 Occurrence Handle1:CAS:528:DyaL1cXhvFOqsrY%3D Occurrence Handle3664496

    CAS  PubMed  Google Scholar 

  5. P. J. Houghton P. J. Cheshire J. C. Hallman M. C. Bissery A. Mathieu-Boue J. A. Houghton (1993) ArticleTitleTherapeutic efficacy of thetopoisomerase I inhibitor 7-ethyl-10-(4-[1-piperidino]-1- piperidino)-carbonyloxy-camptothecin against human tumor xenografts:lack of cross-resistance in vivo in tumors with acquired resistance to the topoisomerase I inhibitor 9-dimethylaminomethyl-10-hydroxycamptothecin Cancer Res. 53 2823–2829 Occurrence Handle1:CAS:528:DyaK3sXltVymsbs%3D Occurrence Handle8504425

    CAS  PubMed  Google Scholar 

  6. M. Potmesil (1994) ArticleTitleCamptothecins: from bench research to hospital wards Cancer Res. 54 1431–1439 Occurrence Handle1:CAS:528:DyaK2c**tVOktbo%3D Occurrence Handle8137244

    CAS  PubMed  Google Scholar 

  7. K. Ota R. Ohno S. Shirakawa T. Masaoka K. Okada Y. Ohashi T. Taguchi (1994) ArticleTitleLate phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies Gan To Kagaku Ryoho 21 1047–1055 Occurrence Handle1:STN:280:ByuB2s%2FotFY%3D Occurrence Handle8210256

    CAS  PubMed  Google Scholar 

  8. Y. Shimizu S. Umezawa K. Hasumi (1996) ArticleTitleSuccessful treatment of clear cell adenocarcinoma of the ovary (OCCA) with a combination of CPT-11 and mitomycin C Gan To Kagaku Ryoho 23 587–593 Occurrence Handle1:STN:280:BymA3cvkvFY%3D Occurrence Handle8678517

    CAS  PubMed  Google Scholar 

  9. C. F. Verschraegen T. Levy A. P. Kudelka E. Llerena K. Ende R. S. Freedman C. L. Edwards M. Hord M. Steger A. L. Kaplan (1997) ArticleTitlePhase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix J. Clin. Oncol. 15 625–631 Occurrence Handle1:CAS:528:DyaK2sXhsVams78%3D Occurrence Handle9053486

    CAS  PubMed  Google Scholar 

  10. W. P. Irvin F. V. Price H. Bailey M. Gelder R. Rosenbluth H. J. Durivage R. K. Potkul (1998) ArticleTitleA phase II study of irinotecan (CPT-11) in patients with advanced squamous cell carcinoma of the cervix Cancer 82 328–333 Occurrence Handle1:CAS:528:DyaK1cXlslymsw%3D%3D Occurrence Handle9445190

    CAS  PubMed  Google Scholar 

  11. S. Kudoh Y. Fujiwara Y. Takada H. Yamamoto A. Kinoshita Y. Ariyoshi K. Furuse M. Fukuoka (1998) ArticleTitlePhase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group J. Clin. Oncol. 16 1068–1074 Occurrence Handle1:CAS:528:DyaK1c**tVKitrs%3D Occurrence Handle9508192

    CAS  PubMed  Google Scholar 

  12. T. Tsuji N. Kaneda K. Kado T. Yokokura T. Yoshimoto D. Tsuru (1991) ArticleTitleCPT-11 converting enzyme from rat serum: purification and some properties J. Pharmacobio-dyn. 14 341–349 Occurrence Handle1:CAS:528:DyaK3MXlsFels70%3D Occurrence Handle1783980

    CAS  PubMed  Google Scholar 

  13. T. Satoh M. Hosokawa R. Atsumi W. Suzuki H. Hakusui E. Nagai (1994) ArticleTitleMetabolic activation of CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin, a novel antitumor agent, by carboxylesterase Biol. Pharm. Bull. 17 662–664 Occurrence Handle1:STN:280:ByqD3cvisVQ%3D Occurrence Handle7920428

    CAS  PubMed  Google Scholar 

  14. L. P. Rivory M. R. Bowles J. Robert S. M. Pond (1996) ArticleTitleConversion of irinotecan (CPT-11) to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), by human liver carboxylesterase Biochem. Pharmacol. 52 1103–1111 Occurrence Handle1:CAS:528:DyaK28XmtVKrs78%3D Occurrence Handle8831730

    CAS  PubMed  Google Scholar 

  15. R. Humerickhouse K. Lohrbach L. Li W. F. Bosron M. E. Dolan (2000) ArticleTitleCharacterization of CPT-11 hydrolysis by human liver carboxylesterase isoforms hCE-1 and hCE-2 Cancer Res. 60 1189–1192 Occurrence Handle1:CAS:528:DC%2BD3cXhvFWrsb8%3D Occurrence Handle10728672

    CAS  PubMed  Google Scholar 

  16. S. Bencharit C. L. Morton E. L. Howard-Williams M. K. Danks P. M. Potter M. R. Redinbo (2002) ArticleTitleStructural insights into CPT-11 activation by mammalian carboxylesterases Nat. Struct. Biol. 9 337–342 Occurrence Handle1:CAS:528:DC%2BD38XjtFyrs74%3D Occurrence Handle11967565

    CAS  PubMed  Google Scholar 

  17. T. Itoh I. Takemoto S. Itagaki K. Sasaki T. Hirano K. Iseki (2004) ArticleTitleBiliary excretion of irinotecan and its metabolites J. Pharm. Pharm. Sci. 7 13–18 Occurrence Handle1:CAS:528:DC%2BD2cXktFGit7w%3D Occurrence Handle15144730

    CAS  PubMed  Google Scholar 

  18. Y. Kawato M. Aonuma Y. Hirota H. Kuga K. Sato (1991) ArticleTitleIntracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11 Cancer Res. 51 4187–4191 Occurrence Handle1:CAS:528:DyaK3MXlsV2rurs%3D Occurrence Handle1651156

    CAS  PubMed  Google Scholar 

  19. R. H. Mathijssen R. J. Alphen Particlevan J. Verweij W. J. Loos K. Nooter G. Stoter A. Sparreboom (2001) ArticleTitleClinical pharmacokinetics and metabolism of irinotecan (CPT-11) Clin. Cancer Res. 7 2182–2194 Occurrence Handle1:CAS:528:DC%2BD3MXmsVOmsbg%3D Occurrence Handle11489791

    CAS  PubMed  Google Scholar 

  20. A. Santos S. Zanetta T. Cresteil A. Deroussent F. Pein E. Raymond L. Vernillet M. L. Risse V. Boige A. Gouyette (2000) ArticleTitleMetabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans Clin. Cancer Res. 6 2012–2020 Occurrence Handle1:CAS:528:DC%2BD3cXktVWitr4%3D Occurrence Handle10815927

    CAS  PubMed  Google Scholar 

  21. K. Arimori N. Kuroki A. Kumamoto N. Tanoue M. Nakano E. Kumazawa A. Tohgo M. Kikuchi (2001) ArticleTitleExcretion into gastrointestinal tract of irinotecan lactone and carboxylate forms and their pharmacodynamics in rodents Pharm. Res. 18 814–822 Occurrence Handle1:CAS:528:DC%2BD3MXlt1Cqtbc%3D Occurrence Handle11474786

    CAS  PubMed  Google Scholar 

  22. N. Hanioka S. Ozawa H. **no M. Ando Y. Saito J. Sawada (2001) ArticleTitleHuman liver UDP-glucuronosyltransferase isoforms involved in the glucuronidation of 7-ethyl-10-hydroxycamptothecin Xenobiotica 31 687–699 Occurrence Handle1:CAS:528:DC%2BD3MXotVKjtbc%3D Occurrence Handle11695848

    CAS  PubMed  Google Scholar 

  23. L. P. Rivory J. F. Riou M. C. Haaz S. Sable M. Vuilhorgne A. Commercon S. M. Pond J. Robert (1996) ArticleTitleIdentification and properties of a major plasma metabolite of irinotecan (CPT-11) isolated from the plasma of patients Cancer Res. 56 3689–3694 Occurrence Handle1:CAS:528:DyaK28XltVKksrc%3D Occurrence Handle8706009

    CAS  PubMed  Google Scholar 

  24. L. P. Rivory M. C. Haaz P. Canal F. Lokiec J. P. Armand J. Robert (1997) ArticleTitlePharmacokinetic interrelationships of irinotecan (CPT-11) and its three major plasma metabolites in patients enrolled in phase I/II trials Clin. Cancer Res. 3 1261–1266 Occurrence Handle1:CAS:528:DyaK2sXls1Smtrw%3D Occurrence Handle9815808

    CAS  PubMed  Google Scholar 

  25. M. C. Haaz L. Rivory C. Riche L. Vernillet J. Robert (1998) ArticleTitleMetabolism of irinotecan (CPT-11) by human hepatic microsomes: participation of cytochrome P-450 3A and drug interactions Cancer Res. 58 468–472 Occurrence Handle1:STN:280:DyaK1c7hslaqtw%3D%3D Occurrence Handle9458091

    CAS  PubMed  Google Scholar 

  26. A. Santos S. Zannetta T. Cresteil (2000) ArticleTitleMetabolism of action of camptothecin Ann. N.Y. Acad. Sci. 922 1–10 Occurrence Handle11193884

    PubMed  Google Scholar 

  27. C. Farabos M. C. Haaz P. Gires J. Robert (2001) ArticleTitleHepatic extraction, metabolism, and biliary excretion of irinotecan in the isolated perfused rat liver J. Pharm. Sci. 90 722–731 Occurrence Handle1:CAS:528:DC%2BD3MXksFequ70%3D Occurrence Handle11357175

    CAS  PubMed  Google Scholar 

  28. E. Gupta T. M. Lestingi R. Mick J. Ramirez E. E. Vokes M. J. Ratain (1994) ArticleTitleMetabolic fate of irinotecan in humans: correlationof glucuronidation with diarrhea Cancer Res. 54 3723–3725 Occurrence Handle1:STN:280:ByuA3cnjslI%3D Occurrence Handle8033091

    CAS  PubMed  Google Scholar 

  29. Y. Sugiyama Y. Kato X. Chu (1998) ArticleTitleMultiplicity of biliary excretion mechanisms for the camptothecin derivative irinotecan (CPT-11), its metabolite SN-38, and its glucuronide: role of canalicular multispecific organic anion transporter and P-glycoprotein Cancer Chemother. Pharmacol. 42 S44–S49 Occurrence Handle1:CAS:528:DyaK1cXlvV2mur8%3D Occurrence Handle9750028

    CAS  PubMed  Google Scholar 

  30. D. Gandia D. Abigerges J. P. Armand G. Chabot L. Costa ParticleDa M. Forni ParticleDe A. Mathieu-Boue P. Herait (1993) ArticleTitleCPT-11-induced cholinergic effects in cancer patients J. Clin. Oncol. 11 196–197 Occurrence Handle1:STN:280:ByyC3Mrnslc%3D Occurrence Handle8418235

    CAS  PubMed  Google Scholar 

  31. J. R. Hecht (1998) ArticleTitleGastrointestinal toxicity or irinotecan Oncology (Huntingt) 12 72–78 Occurrence Handle1:STN:280:DyaK1czpsVWmuw%3D%3D

    CAS  Google Scholar 

  32. L. F. Liu S. D. Desai T. K. Li (2000) ArticleTitleMechanism of action of camptothecin Ann. N.Y. Acad. Sci. 922 1–10 Occurrence Handle11193884

    PubMed  Google Scholar 

  33. Y. Xu M. A. Villalona-Calero (2002) ArticleTitleIrinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity Ann. Oncol. 13 1841–1851 Occurrence Handle1:STN:280:DC%2BD38nptF2nsQ%3D%3D Occurrence Handle12453851

    CAS  PubMed  Google Scholar 

  34. S. Kornblau A. B. Benson R. Catalano R. E. Champlin C. Engelking M. Field C. Ippoliti H. M. Lazarus E. Mitchell J. Rubin (2000) ArticleTitleManagement of cancer treatment-related diarrhea. Issues and therapeutic strategies J. Pain Symptom Manag. 19 118–129 Occurrence Handle1:STN:280:DC%2BD3c7msVOksg%3D%3D

    CAS  Google Scholar 

  35. H. Sakai T. Sato N. Hamada M. Yasue A. Ikari B. Kakinoki N. Takeguchi (1997) ArticleTitleThromboxane A2, released by the anti-tumour drug irinotecan, is a novel stimulator of Cl-secretion in isolated rat colon J. Physiol. 505 IssueIDPt. 1 133–144 Occurrence Handle1:CAS:528:DyaK2sXotVGmsbs%3D Occurrence Handle9409477

    CAS  PubMed  Google Scholar 

  36. T. Suzuki H. Sakai A. Ikari (2000) ArticleTitleInhibition of thromboxane A2-induced Cl-secretion by antidiarrhea drug loperamide inisolated rat colon J. Pharmacol. Exp. Ther. 295 233–238 Occurrence Handle1:CAS:528:DC%2BD3cXnt1ygu70%3D Occurrence Handle10991984

    CAS  PubMed  Google Scholar 

  37. F. Saliba R. Hagipantelli J. L. Misset G. Bastian G. Vassal M. Bonnay P. Herait C. Cote M. Mahjoubi D. Mignard (1998) ArticleTitlePathophysiology and therapy of irinotecan-induced delayed-onset diarrhea in patients with advanced colorectal cancer: a prospective assessment J. Clin. Oncol. 16 2745–2751 Occurrence Handle1:CAS:528:DyaK1cXlsFCgu7o%3D Occurrence Handle9704727

    CAS  PubMed  Google Scholar 

  38. T. Ikegami L. Ha K. Arimori P. Latham K. Kobayashi S. Ceryak Y. Matsuzaki B. Bouscarel (2002) ArticleTitleIntestinal alkalization as a possible preventive mechanism in irinotecan (CPT-11)-induced diarrhea Cancer Res. 62 179–187 Occurrence Handle1:CAS:528:DC%2BD38XntV2hsg%3D%3D Occurrence Handle11782376

    CAS  PubMed  Google Scholar 

  39. H. Shinohara J. J. Killion H. Kuniyasu R. Kumar I. J. Fidler (1998) ArticleTitlePrevention of intestinal toxic effects and intensification of irinotecan’s therapeutic efficacy against murine colon cancer liver metastases by oral administration of the lipopeptide JBT 3002 Clin. Cancer Res. 4 2053–2063 Occurrence Handle1:CAS:528:DyaK1cXmslCjsrY%3D Occurrence Handle9748119

    CAS  PubMed  Google Scholar 

  40. K. Takasuna T. Hagiwara M. Hirohashi M. Kato M. Nomura E. Nagai T. Yokoi T. Kamataki (1998) ArticleTitleInhibition of intestinal microflora beta-glucuronidase modifies the distribution of the active metabolite of the antitumor agent, irinotecan hydrochloride (CPT-11) in rats Cancer Chemother. Pharmacol. 42 280–286 Occurrence Handle1:CAS:528:DyaK1cXls1Wlt7c%3D Occurrence Handle9744772

    CAS  PubMed  Google Scholar 

  41. D. F. Kehrer A. Sparreboom J. Verweij P. Bruijn Particlede C. A. Nierop J. Schraaf Particlevan de E. J. Ruijgrok M. J. Jonge Particlede (2001) ArticleTitleModulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients Clin. Cancer Res. 7 1136–1141 Occurrence Handle1:CAS:528:DC%2BD3MXktlemurY%3D Occurrence Handle11350876

    CAS  PubMed  Google Scholar 

  42. M. Prados J. Kuhn W. Yung (2001) ArticleTitleA phase-I study of CPT-11 given every 3 weeks to patients with recurrent malignant glioma. A North American Brain Tumor Consortium (NABTC) study Proc. -Am. Soc. Clin. Oncol. 19 162

    Google Scholar 

  43. E. Gupta A. Safa X. Wang M. Ratain (1996) ArticleTitlePharmacokinetic modulation of irinotecan and metabolites by cyclosporin A Cancer Res. 56 1309–1314 Occurrence Handle1:CAS:528:DyaK28XhsFGntrg%3D Occurrence Handle8640819

    CAS  PubMed  Google Scholar 

  44. M. Ratain (2000) ArticleTitleInsights into the pharmacokinetics and pharmacodynamics of irinotecan Clin. Cancer Res. 6 3393–3394 Occurrence Handle1:STN:280:DC%2BD3cvkslWntQ%3D%3D Occurrence Handle10999719

    CAS  PubMed  Google Scholar 

  45. O. C. Trifan W. F. Durham V. S. Salazar J. Horton B. D. Levine B. S. Zweifel T. W. Davis J. L. Masferrer (2002) ArticleTitleCyclooxygenase-2 inhibition with celecoxib enhances antitumor efficacy and reduces diarrhea side effect of CPT-11 Cancer Res. 62 5778–5784 Occurrence Handle1:CAS:528:DC%2BD38XotFyktrs%3D Occurrence Handle12384538

    CAS  PubMed  Google Scholar 

  46. M. Horikawa Y. Kato Y. Sugiyama (2002) ArticleTitleReduced gastrointestinal toxicity following inhibition of the biliary excretion of irinotecan and its metabolites by probenecid in rats Pharm. Res. 19 1345–1353 Occurrence Handle1:CAS:528:DC%2BD38XntlSjsLY%3D Occurrence Handle12403072

    CAS  PubMed  Google Scholar 

  47. M. Horikawa Y. Kato Y. Sugiyama (2002) ArticleTitleReduced gastrointestinal toxicity following inhibition of the biliary excretion of irinotecan and its metabolites by probenecid in rats Pharm. Res. 19 1345–1353 Occurrence Handle1:CAS:528:DC%2BD38XntlSjsLY%3D Occurrence Handle12403072

    CAS  PubMed  Google Scholar 

  48. G. Carlo ParticleDi F. Borrelli E. Ernst A. A. Izzo (2001) ArticleTitleSt. John’s wort: prozac from the plant kingdom Trends Pharmacol. Sci. 22 292–297 Occurrence Handle11395157

    PubMed  Google Scholar 

  49. A. R. Bilia S. Gallori F. F. Vincieri (2002) ArticleTitleSt. John’s wort and depression: efficacy, safety and tolerability-an update Life Sci. 70 3077–3096 Occurrence Handle1:CAS:528:DC%2BD38XjsVSrtLc%3D Occurrence Handle12008092

    CAS  PubMed  Google Scholar 

  50. V. Schulz (2002) ArticleTitleClinical trials with hypericum extracts in patients with depression-results, comparisons, conclusions for therapy with antidepressant drugs Phytomedicine 9 468–474 Occurrence Handle12222670

    PubMed  Google Scholar 

  51. E. Ernst (1999) ArticleTitleSecond thoughts about safety of St. John’s wort Lancet 354 2014–2016 Occurrence Handle1:STN:280:DC%2BD3c7gtVeitA%3D%3D Occurrence Handle10636361

    CAS  PubMed  Google Scholar 

  52. A. Johne J. Brockmoller S. Bauer A. Maurer M. Langheinrich I. Roots (1999) ArticleTitlePharmacokinetic interaction of digoxin with an herbal extract from St. John’s wort (Hypericum perforatum) Clin. Pharmacol. Ther. 66 338–345 Occurrence Handle1:CAS:528:DyaK1MXntlWiu7o%3D Occurrence Handle10546917

    CAS  PubMed  Google Scholar 

  53. D. Durr B. Stieger G. A. Kullak-Ublick K. M. Rentsch H. C. Steinert P. J. Meier K. Fattinger (2000) ArticleTitleSt. John’s Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4 Clin. Pharmacol. Ther. 68 598–604 Occurrence Handle1:CAS:528:DC%2BD3MXht1Sjs7Y%3D Occurrence Handle11180019

    CAS  PubMed  Google Scholar 

  54. L. B. Moore B. Goodwin S. A. Jones G. B. Wisely C. J. Serabjit-Singh T. M. Willson (2000) ArticleTitleSt. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor Proc. Natl. Acad. Sci. USA 97 7500–7502 Occurrence Handle1:CAS:528:DC%2BD3cXksVKhs7s%3D Occurrence Handle10852961

    CAS  PubMed  Google Scholar 

  55. S. C. Piscitelli A. H. Burstein D. Chaitt R. M. Alfaro J. Falloon (2000) ArticleTitleIndinavir concentrations and St. John’s wort Lancet 355 547–548 Occurrence Handle1:CAS:528:DC%2BD3cXhs1elsbs%3D Occurrence Handle10683007

    CAS  PubMed  Google Scholar 

  56. C. A. Roby G. D. Anderson E. Kantor D. A. Dryer A. H. Burstein (2000) ArticleTitleSt. John’s wort: effect on CYP3A4 activity Clin. Pharmacol. Ther. 67 451–457 Occurrence Handle1:CAS:528:DC%2BD3cXktVCmsbk%3D Occurrence Handle10824623

    CAS  PubMed  Google Scholar 

  57. F. Ruschitzka P. J. Meier M. Turina T. F. Luscher G. Noll (2000) ArticleTitleAcute heart transplant rejection due to Saint John’s wort Lancet 355 548–549 Occurrence Handle1:STN:280:DC%2BD3c7ksFaisQ%3D%3D Occurrence Handle10683008

    CAS  PubMed  Google Scholar 

  58. J. M. Wentworth M. Agostini J. Love J. W. Schwabe V. K. Chatterjee (2000) ArticleTitleSt. John’s wort, a herbal antidepressant, activates the steroid X receptor J. Endocrinol. 166 R11–R16 Occurrence Handle1:CAS:528:DC%2BD3cXmslyls78%3D Occurrence Handle10974665

    CAS  PubMed  Google Scholar 

  59. B. Goodwin L. B. Moore C. M. Stoltz D. D. McKee S. A. Kliewer (2001) ArticleTitleRegulation of the human CYP2B6 gene by the nuclear pregnane X receptor Mol. Pharmacol. 60 427–431 Occurrence Handle1:CAS:528:DC%2BD3MXmtFantbs%3D Occurrence Handle11502872

    CAS  PubMed  Google Scholar 

  60. Z. Q. Wang C. Gorski M. A. Hamman S. M. Huang L. J. Lesko S. D. Hall (2001) ArticleTitleThe effects of St. John’s wort (Hypericum Perforatum) on human cytochrome P450 activity Clin. Pharmacol. Ther. 70 317–326 Occurrence Handle1:STN:280:DC%2BD3MrmslShtw%3D%3D Occurrence Handle11673747

    CAS  PubMed  Google Scholar 

  61. A. Johne J. Schmider J. Brockmoller A. M. Stadelmann E. Stormer S. Bauer G. Scholler M. Langheinrich I. Roots (2002) ArticleTitleDecreased plasma levels of amitriptyline and its metabolites on comedication with an extract from St. John’s wort (Hypericum perforatum) J. Clin. Psychopharmacol. 22 46–54 Occurrence Handle1:CAS:528:DC%2BD38Xht1yku7s%3D Occurrence Handle11799342

    CAS  PubMed  Google Scholar 

  62. Z. Wang M. A. Hamman S. M. Huang L. J. Lesko S. D. Hall (2002) ArticleTitleEffect of St. John’s wort on the pharmacokinetics of fexofenadine Clin. Pharmacol. Ther. 71 414–420 Occurrence Handle1:CAS:528:DC%2BD38XlslCktrk%3D Occurrence Handle12087344

    CAS  PubMed  Google Scholar 

  63. A. A. Izzo (2004) ArticleTitleDrug interactions with St. John’s Wort (Hypericum perforatum): a review of the clinical evidence Int. J. Clin. Pharmacol. Ther. 42 139–148 Occurrence Handle1:CAS:528:DC%2BD2c**sFKrurw%3D Occurrence Handle15049433

    CAS  PubMed  Google Scholar 

  64. S. Zhou E. Chan S. Q. Pan M. Huang E. J. Lee (2004) ArticleTitlePharmacokinetic interactions of drugs with St. John’s wort J. Psychopharmacol. 18 262–276 Occurrence Handle1:CAS:528:DC%2BD2cXms1ahur4%3D Occurrence Handle15260917

    CAS  PubMed  Google Scholar 

  65. R. H. Mathijssen J. Verweij P. Bruijn Particlede W. J. Loos A. Sparreboom (2002) ArticleTitleEffects of St. John’s wort on irinotecan metabolism J. Natl. Cancer Inst. 94 1247–1249 Occurrence Handle1:CAS:528:DC%2BD38XntVyjsL8%3D Occurrence Handle12189228

    CAS  PubMed  Google Scholar 

  66. A. Kurita S. Kado N. Kaneda M. Onoue S. Hashimoto T. Yokokura (2003) ArticleTitleAlleviation of side effects induced by irinotecan hydrochloride (CPT-11) in rats by intravenous infusion Cancer Chemother. Pharmacol. 52 349–360 Occurrence Handle12904895

    PubMed  Google Scholar 

  67. A. Kurita S. Kado N. Kaneda M. Onoue S. Hashimoto T. Yokokura (2000) ArticleTitleModified irinotecan hydrochloride (CPT-11) administration schedule improves induction of delayed-onset diarrhea in rats Cancer Chemother. Pharmacol. 46 211–220 Occurrence Handle1:CAS:528:DC%2BD3cXlvFOqsb8%3D Occurrence Handle11021738

    CAS  PubMed  Google Scholar 

  68. M. Miampamba E. J. Parr D. M. McCafferty J. L. Wallace K. A. Sharkey (1998) ArticleTitleEffect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat Aliment Pharmacol. Ther. 12 219–228 Occurrence Handle1:CAS:528:DyaK1c**slejsrg%3D Occurrence Handle9570256

    CAS  PubMed  Google Scholar 

  69. M. Kruschewski T. Foitzik A. Perez-Canto A. Hubotter H. J. Buhr (2001) ArticleTitleChanges of colonic mucosal microcirculation and histology in two colitis models: an experimental study using intravital microscopy and a new histological scoring system Dig. Dis. Sci. 46 2336–2343 Occurrence Handle1:STN:280:DC%2BD3MnmvVGmsQ%3D%3D Occurrence Handle11713932

    CAS  PubMed  Google Scholar 

  70. I. Maric L. Poljak S. Zoricic D. Bobinac D. Bosukonda K. T. Sampath S. Vukicevic (2003) ArticleTitleBone morphogenetic protein-7 reduces the severity of colon tissue damage and accelerates the healing of inflammatory bowel disease in rats J. Cell. Physiol. 196 258–264 Occurrence Handle1:CAS:528:DC%2BD3sXltlSmsbw%3D Occurrence Handle12811818

    CAS  PubMed  Google Scholar 

  71. A. Sparreboom P. Bruijn Particlede M. J. Jonge Particlede W. J. Loos G. Stoter J. Verweij K. Nooter (1998) ArticleTitleLiquid chromatographic determination of irinotecan and three major metabolites in human plasma, urine and feces J. Chromatogr., B, Biomed. Sci. Appl. 712 225–235

    Google Scholar 

  72. J. Escoriaza A. Aldaz C. Castellanos E. Calvo J. Giraldez (2000) ArticleTitleSimple and rapid determination of irinotecan and its metabolite SN-38 in plasma by high-performance liquid-chromatography: application to clinical pharmacokinetic studies J. Chromatogr., B, Biomed. Sci. Appl. 740 159–168

    Google Scholar 

  73. S. Poujol F. **uet F. Malosse C. Astre M. Ychou S. Culine F. Bressolle (2003) ArticleTitleSensitive HPLC-fluorescence method for irinotecan and four major metabolites in human plasma and saliva: application to pharmacokinetic studies Clin. Chem. 49 1900–1908 Occurrence Handle1:CAS:528:DC%2BD3sXosleqsL0%3D Occurrence Handle14578322

    CAS  PubMed  Google Scholar 

  74. D. Durr B. Stieger G. A. Kullak-Ublick K. M. Rentsch H. C. Steinert P. J. Meier K. Fattinger (2000) ArticleTitleSt. John’s wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4 Clin. Pharmacol. Ther. 68 598–604 Occurrence Handle1:CAS:528:DC%2BD3MXht1Sjs7Y%3D Occurrence Handle11180019

    CAS  PubMed  Google Scholar 

  75. Y. Shibayama R. Ikeda T. Motoya K. Yamada (2004) ArticleTitleSt. John’s Wort (Hypericum perforatum) induces overexpression of multidrug resistance protein 2 (MRP2) in rats: a 30-day ingestion study Food Chem. Toxicol. 42 995–1002 Occurrence Handle1:CAS:528:DC%2BD2cXjsVWhsbg%3D Occurrence Handle15110109

    CAS  PubMed  Google Scholar 

  76. M. L. Wong, F. O’Kirwan, J. P. Hannestad, K. J. Irizarry, D. Elashoff, and J. Licinio. St. John’s wort and imipramine-induced gene expression profiles identify cellular functions relevant to antidepressant action and novel pharmacogenetic candidates for the phenotype of antidepressant treatment response. Mol Psychiatry in press (2004).

  77. O. C. Trifan W. F. Durham V. S. Salazar J. Horton B. D. Levine B. S. Zweifel T. W. Davis J. L. Masferrer (2002) ArticleTitleCyclooxygenase-2 inhibition with celecoxib enhances antitumor efficacy and reduces diarrhea side effect of CPT-11 Cancer Res. 62 5778–5784 Occurrence Handle1:CAS:528:DC%2BD38XotFyktrs%3D Occurrence Handle12384538

    CAS  PubMed  Google Scholar 

  78. K. Arimori N. Kuroki M. Hidaka T. Iwakiri K. Yamsaki M. Okumura H. Ono N. Takamura M. Kikuchi M. Nakano (2003) ArticleTitleEffect of P-glycoprotein modulator, cyclosporin A, on the gastrointestinal excretion of irinotecan and its metabolite SN-38 in rats Pharm. Res. 20 910–917 Occurrence Handle1:CAS:528:DC%2BD3sXjvFyis7g%3D Occurrence Handle12817897

    CAS  PubMed  Google Scholar 

  79. B. Chowbay A. Sharma Q. Y. Zhou Y. B. Cheung E. J. Lee (2003) ArticleTitleThe modulation of irinotecan-induced diarrhoea and pharmacokinetics by three different classes of pharmacologic agents Oncol. Rep. 10 745–751 Occurrence Handle1:CAS:528:DC%2BD3sXjsVOltb4%3D Occurrence Handle12684653

    CAS  PubMed  Google Scholar 

  80. A. Kurita S. Kado N. Kaneda M. Onoue S. Hashimoto T. Yokokura (2003) ArticleTitleAlleviation of side effects induced by irinotecan hydrochloride (CPT-11) in rats by intravenous infusion Cancer Chemother. Pharmacol. 52 349–356 Occurrence Handle12904895

    PubMed  Google Scholar 

  81. J. F. Pizzolato L. B. Saltz (2003) ArticleTitleThe camptothecins Lancet 361 2235–2242 Occurrence Handle10.1016/S0140-6736(03)13780-4 Occurrence Handle1:CAS:528:DC%2BD3sXkvFelsbc%3D Occurrence Handle12842380

    Article  CAS  PubMed  Google Scholar 

  82. M. D. DeMario M. J. Ratain (1998) ArticleTitleOral chemotherapy-Rationale and future directions J. Clin. Oncol. 16 2557–2567 Occurrence Handle1:CAS:528:DyaK1cXks1GnurY%3D Occurrence Handle9667278

    CAS  PubMed  Google Scholar 

  83. F. A. Greco (1998) ArticleTitleEvolving role of oral chemotherapy for the treatment of patients with neoplasms Oncology 12 43–50 Occurrence Handle1:STN:280:DyaK1c3hslGhuw%3D%3D

    CAS  Google Scholar 

  84. J. M. M. Terwogt J. H. M. Schellens W. W. T. Huinink J. H. Beijnen (1999) ArticleTitleClinical pharmacology of anticancer agents in relation to formulations and administration routes Cancer Treat. Rev. 25 83–101 Occurrence Handle1:CAS:528:DyaK1MXlsFGnt7Y%3D Occurrence Handle10395834

    CAS  PubMed  Google Scholar 

  85. C. F. Stewart W. C. Zamboni W. R. Crom P. J. Houghton (1997) ArticleTitleDisposition of irinotecan and SN-38 following oral and intravenous irinotecan dosing in mice Cancer Chemother. Pharmacol. 40 259–265 Occurrence Handle1:CAS:528:DyaK2sXjvF2kurY%3D Occurrence Handle9219511

    CAS  PubMed  Google Scholar 

  86. W. C. Zamboni P. J. Houghton J. Thompson P. J. Cheshire S. K. Hanna L. B. Richmond X. Lou C. F. Stewart (1998) ArticleTitleAltered irinotecan and SN-38 disposition after intravenous andoral administration of irinotecan in mice bearing human neuroblastoma xenografts Clin. Cancer Res. 4 455–462 Occurrence Handle1:CAS:528:DyaK1cXhtlSmtro%3D Occurrence Handle9516936

    CAS  PubMed  Google Scholar 

  87. R. L. Drengler J. G. Kuhn L. J. Schaaf G. I. Rodriguez M. A. Villalona-Calero L. A. Hammond J. A. Stephenson SuffixJr S. Hodges M. A. Kraynak B. A. Staton (1999) ArticleTitlePhase I and pharmacokinetic trial of oral irinotecan administered daily for 5 days every 3 weeks in patients with solid tumors J. Clin. Oncol. 17 685–696 Occurrence Handle1:CAS:528:DyaK1MXht1Wlsr0%3D Occurrence Handle10080615

    CAS  PubMed  Google Scholar 

  88. C. F. Stewart M. Leggas J. D. Schuetz J. C. Panetta P. J. Cheshire J. Peterson N. Daw J. J. Jenkins SuffixIII R. Gilbertson G. S. Germain (2004) ArticleTitleGefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice Cancer Res. 64 7491–7499 Occurrence Handle1:CAS:528:DC%2BD2cXosFynurg%3D Occurrence Handle15492275

    CAS  PubMed  Google Scholar 

  89. N. E. Schoemaker I. E. Kuppens W. W. Huinink P. Lefebvre J. H. Beijnen S. Assadourian G. J. Sanderink J. H. Schellens (2005) ArticleTitlePhase I study of an oral formulation of irinotecan administered daily for 14 days every 3 weeks in patients with advanced solid tumours Cancer Chemother. Pharmacol. 55 263–270 Occurrence Handle1:CAS:528:DC%2BD2MXhtVCnsQ%3D%3D Occurrence Handle15592838

    CAS  PubMed  Google Scholar 

  90. O. Soepenberg H. Dumez J. Verweij D. Semiond M. J. Dejonge F. A. Eskens J. T. Steeg J. Selleslach S. Assadourian G. J. Sanderink (2005) ArticleTitlePhase I and pharmacokinetic study of oral irinotecan given once daily for 5 days every 3 weeks in combination with capecitabine in patients with solid tumors J. Clin. Oncol. 23 889–898 Occurrence Handle1:CAS:528:DC%2BD2M**tVKitL4%3D Occurrence Handle15681535

    CAS  PubMed  Google Scholar 

  91. J. S. Markowitz C. L. DeVane D. W. Boulton S. W. Carson Z. Nahas S. C. Risch (2000) ArticleTitleEffect of St. John’s wort (Hypericum perforatum) on cytochrome P-450 2D6 and 3A4 activity in healthy volunteers Life Sci. 66 PL133–PL139 Occurrence Handle1:CAS:528:DC%2BD3cXmvFOjug%3D%3D Occurrence Handle10698361

    CAS  PubMed  Google Scholar 

  92. J. S. Markowitz J. L. Donovan C. L. DeVane R. M. Taylor Y. Ruan J. S. Wang K. D. Chavin (2003) ArticleTitleEffect of St. John’s wort on drug metabolism by induction of cytochrome P450 3A4 enzyme JAMA 290 1500–1504 Occurrence Handle1:CAS:528:DC%2BD3sXntlCmsbg%3D Occurrence Handle13129991

    CAS  PubMed  Google Scholar 

  93. X. Y. Chu Y. Kato K. Niinuma K. I. Sudo H. Hakusui Y. Sugiyama (1997) ArticleTitleMultispecific organic anion transporter is responsible for the biliary excretion of the camptothecin derivative irinotecan and its metabolites in rats J. Pharmacol. Exp. Ther. 281 304–314 Occurrence Handle1:CAS:528:DyaK2s**slSrsL4%3D Occurrence Handle9103511

    CAS  PubMed  Google Scholar 

  94. X. Y. Chu Y. Kato Y. Sugiyama (1997) ArticleTitleMultiplicity of biliary excretion mechanisms for irinotecan, CPT-11, and its metabolites in rats Cancer Res. 57 1934–1938 Occurrence Handle1:CAS:528:DyaK2sXjtlGkt74%3D Occurrence Handle9157988

    CAS  PubMed  Google Scholar 

  95. X. Y. Chu H. Suzuki K. Ueda Y. Kato S. Akiyama Y. Sugiyama (1999) ArticleTitleActive efflux of CPT-11 and its metabolites in human KB-derived cell lines J. Pharmacol. Exp. Ther. 288 735–741 Occurrence Handle1:CAS:528:DyaK1MXpvFOmtg%3D%3D Occurrence Handle9918583

    CAS  PubMed  Google Scholar 

  96. M. Yoshikawa Y. Ikegami S. Hayasaka K. Ishii A. Ito K. Sano T. Suzuki T. Togawa H. Yoshida H. Soda (2004) ArticleTitleNovel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells Int. J. Cancer 110 921–927 Occurrence Handle1:CAS:528:DC%2BD2cXkvFCmtLg%3D Occurrence Handle15170677

    CAS  PubMed  Google Scholar 

  97. M. Yoshikawa Y. Ikegami K. Sano H. Yoshida H. Mitomo S. Sawada T. Ishikawa (2004) ArticleTitleTransport of SN-38 by the wild type of human ABC transporter ABCG2 and its inhibition by quercetin, a natural flavonoid J. Exp. Ther. Oncol. 4 25–35 Occurrence Handle1:CAS:528:DC%2BD2cXktlKitLk%3D Occurrence Handle15255290

    CAS  PubMed  Google Scholar 

  98. J. Barnes L. A. Anderson J. D. Phillipson (2001) ArticleTitleSt. John’s wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties J. Pharm. Pharmacol. 53 583–600 Occurrence Handle1:CAS:528:DC%2BD3MXktVWlsbc%3D Occurrence Handle11370698

    CAS  PubMed  Google Scholar 

  99. E. Tedeschi M. Menegazzi D. Margotto H. Suzuki U. Forstermann H. Kleinert (2003) ArticleTitleAnti-inflammatory actions of St. John’s wort: inhibition of human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1alpha (STAT-1alpha) activation J. Pharmacol. Exp. Ther. 307 254–261 Occurrence Handle1:CAS:528:DC%2BD3sXnslGkurc%3D Occurrence Handle12954801

    CAS  PubMed  Google Scholar 

  100. P. M. Bork S. Bacher M. L. Schmitz U. Kaspers M. Heinrich (1999) ArticleTitleHypericin as a non-antioxidant inhibitor of NF-kappa B Planta Med. 65 297–300 Occurrence Handle1:CAS:528:DyaK1MXjtlOjur8%3D Occurrence Handle10364831

    CAS  PubMed  Google Scholar 

  101. P. Agostinis A. Donella-Deana J. Cuveele A. Vandenbogaerde S. Sarno W. Merlevede P. Witte Particlede (1996) ArticleTitleA comparative analysis of the photosensitized inhibition of growth-factor regulated protein kinases by hypericin-derivatives Biochem. Biophys. Res. Commun. 220 613–617 Occurrence Handle1:CAS:528:DyaK28**t1Kmsro%3D Occurrence Handle8607812

    CAS  PubMed  Google Scholar 

  102. B. L. Fiebich A. Hollig K. Lieb (2001) ArticleTitleInhibition of substance P-induced cytokine synthesis by St. John’s wort extracts Pharmacopsychiatry 34 S26–S28 Occurrence Handle1:CAS:528:DC%2BD3MXmt1ansLs%3D Occurrence Handle11518071

    CAS  PubMed  Google Scholar 

  103. G. M. Raso R. Meli G. Carlo ParticleDi M. Pacilio R. Carlo ParticleDi (2001) ArticleTitleInhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids in macrophage J774A. 1 Life Sci. 68 921–931 Occurrence Handle1:CAS:528:DC%2BD3MXlvFKrtA%3D%3D Occurrence Handle11213362

    CAS  PubMed  Google Scholar 

  104. G. M. Raso M. Pacilio G. Carlo ParticleDi E. Esposito L. Pinto R. Meli (2002) ArticleTitleIn-vivo and in-vitro anti-inflammatory effect of Echinacea purpurea and Hypericum perforatum J. Pharm. Pharmacol. 54 1379–1383 Occurrence Handle1:CAS:528:DC%2BD38XovVejs70%3D Occurrence Handle12396300

    CAS  PubMed  Google Scholar 

  105. E. Tedeschi M. Menegazzi D. Margotto H. Suzuki U. Forstermann H. Kleinert (2003) ArticleTitleAnti-inflammatory actions of St. John’s wort: inhibition of human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1alpha (STAT-1alpha) activation J.Pharmacol. Exp. Ther. 307 254–261 Occurrence Handle1:CAS:528:DC%2BD3sXnslGkurc%3D Occurrence Handle12954801

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors appreciate Lichtwer Pharma GmbH for providing SJW control vehicle. This work was funded by the National University of Singapore Academic Research Funds (No. R-148-000-054-112 and R-148-000-047-101).

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  1. Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore

    Ze** Hu, **-Hu-Aff1">Ze** Hu

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  2. **aoxia Yang
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Hu, Z., Yang, X., Ho, P.CL. et al. St. John’s Wort Modulates the Toxicities and Pharmacokinetics of CPT-11 (Irinotecan) in Rats. Pharm Res 22, 902–914 (2005). https://doi.org/10.1007/s11095-005-4585-0

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  • DOI: https://doi.org/10.1007/s11095-005-4585-0

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