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Article
First‐in‐human, phase I/IIa study of CRLX301, a nanoparticle drug conjugate containing docetaxel, in patients with advanced or metastatic solid malignancies
Background This was a phase I/IIa study to investigate the tolerability, efficacy and pharmacokinetics (PK)/ pharmacodynamics (PD) of CRLX301, CDP-based nanoparticle formulation of docetaxel. Methods The study wa...
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Article
Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients
Obesity may alter mononuclear phagocyte system (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships...
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Article
Impact of formulation on the iontophoretic delivery of the FOLFIRINOX regimen for the treatment of pancreatic cancer
Effective treatment of patients with locally advanced pancreatic cancer is a significant unmet clinical need. One major hurdle that exists is inadequate drug delivery due to the desmoplastic stroma and poor va...
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Protocol
Methods and Study Designs for Characterizing the Pharmacokinetics and Pharmacodynamics of Carrier-Mediated Agents
Major advances in carrier-mediated agents (CMAs), which include nanoparticles, nanosomes, and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantage...
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Article
Technetium Tc 99m sulfur colloid phenotypic probe for the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin in women with ovarian cancer
Significant variability in the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin (PLD) exists. PLD undergoes clearance via the mononuclear phagocyte system (MPS). Technetium Tc 99m sulfu...
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Article
Evaluation of the efficiency of tumor and tissue delivery of carrier-mediated agents (CMA) and small molecule (SM) agents in mice using a novel pharmacokinetic (PK) metric: relative distribution index over time (RDI-OT)
The pharmacokinetics (PK) of carrier-mediated agents (CMA) is dependent upon the carrier system. As a result, CMA PK differs greatly from the PK of small molecule (SM) drugs. Advantages of CMAs over SMs includ...
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Article
Population pharmacokinetics of PEGylated liposomal CPT-11 (IHL-305) in patients with advanced solid tumors
To investigate pharmacokinetics (PK) of encapsulated CPT-11, released CPT-11 and the active metabolite SN-38 following administration of IHL-305 and to identify factors that may influence IHL-305 PK.
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Article
Nonaqueous Gel for the Transdermal Delivery of a DTPA Penta-ethyl Ester Prodrug
Diethylenetriamine pentaacetic acid penta-ethyl ester, designated as C2E5, was successfully incorporated into a nonaqueous gel for transdermal delivery. The thermal and rheological properties of a formulation ...
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Article
Phase I and pharmacokinetic study of IHL-305 (PEGylated liposomal irinotecan) in patients with advanced solid tumors
IHL-305 is a novel PEGylated liposome containing irinotecan. This study examined the safety profile and pharmacokinetics of IHL-305 and established the maximum tolerated dose and recommended phase II dose (RP2D).
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Article
Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients
There is significant inter-patient variability in the pharmacokinetics of pegylated liposomal doxorubicin (PLD). Identification of factors affecting the pharmacokinetics of PLD would enable personalization of ...
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Article
Pharmacologic and phenotypic study of docetaxel in patients with ovarian or primary peritoneal cancer
The objectives of this study were to determine whether the midazolam clearance predicted docetaxel pharmacokinetics, CA-125 change, and response and to assess the impact of cytochrome P450 (CYP) 3A5 and ATP-bi...
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Article
Allometric scaling of pegylated liposomal anticancer drugs
Pegylated liposomal formulations contain lipid conjugated to polyethylene glycol. The disposition of encapsulated drug is dictated by the composition of the liposome, thus altering the pharmacokinetic (PK) pro...
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Article
Open AccessDevelopment and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD)
Non-Hodgkin’s lymphoma (NHL) is the sixth most common cause of cancer deaths in the U.S. Most NHLs initially respond well to chemotherapy, but relapse is common and treatment is often limited due to the toxici...
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Article
Plasma and tissue disposition of non-liposomal DB-67 and liposomal DB-67 in C.B-17 SCID mice
Purpose: DB-67 is a silatecan, 7-silyl-modified camptothecin, with enhanced lipophilicity and increased blood stability of the active-lactone ring. The generation of a liposomal formulati...
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Article
Tumor, tissue, and plasma pharmacokinetic studies and antitumor response studies of docetaxel in combination with 9-nitrocamptothecin in mice bearing SKOV-3 human ovarian xenografts
We evaluated the antitumor activity of two different schedules of docetaxel and 9-nitrocamptothecin (9NC) in mice bearing human SKOV-3 ovarian carcinoma xenografts and evaluated the plasma, tissue, and tumor d...
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Article
Disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in relation to ABC transporter genotypes
Purpose: The source of the pharmacokinetic variability of 9-nitrocamptothecin (9NC) and its 9-aminocamptothecin (9AC) metabolite is unknown. ATP-binding cassette (ABC) transporters have been reported to modulate ...
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Article
Clinical and pharmacokinetic study evaluating the effect of food on the disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in patients with solid tumors
Background: 9-Nitrocamptothecin (9NC) is an orally administered camptothecin analogue that has completed phase III trials for pancreatic cancer. In biological matrices, camptothecin analogues exist in equilibrium...
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Article
Phase-I dose escalation and sequencing study of docetaxel and continuous infusion topotecan in patients with advanced malignancies
Anti-tumor activity can often be enhanced with combination therapy in managing patients with metastatic cancer. However, dose sequence and schedule of delivery can alter the pharmacokinetics, toxicity, and ant...
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Article
Phase I study of weekly (day 1 and 8) docetaxel in combination with capecitabine in patients with advanced solid malignancies
Capecitabine in combination with docetaxel given every 3 weeks has shown a high degree of activity in a number of tumor types, but at the expense of significant toxicity. To improve the therapeutic index, we e...
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Article
Control-Relevant Modeling of the Antitumor Effects of 9-Nitrocamptothecin in SCID Mice Bearing HT29 Human Colon Xenografts
The mathematical model structure selected to describe system behavior is at least partially dependent on the proposed use of the model. In this paper, a pharmacokinetic(PK)/pharmacodynamic (PD) model for use i...
