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Clinical Pharmacokinetics in Patients with Spinal Cord Injuries

  • Review Article
  • Clinical Pharmacokinetics and Disease Processes
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Summary

Although spinal cord injury is a catastrophic affliction with numerous victims and a variety of physiological manifestations, the associated disarray in physiology has yet to be systematically or comprehensively studied as a probable cause for altered pharmacokinetics.

A significant increase in the volume of distribution of drugs such as the aminoglycosides (gentamicin, amikacin, tobramycin), which are highly distributed into the extracellular fluid space and minimally biotransformed, may be anticipated in patients with chronic spinal cord injury. Changes in total body clearance have also been observed for some of these medications.

The influence of the pathophysiology of spinal cord injury on gastrointestinal motility appears to be reflected in an impairment in the bioavailability of drugs [theophylline, paracetamol (acetaminophen), doxycycline] which are passively absorbed and which require an intact postprandial gastric emptying to ensure efficient absorption. For theophylline, the impairment in gastrointestinal absorption appears to be directly proportional to both the magnitude of the impairment in gastric emptyting and to the neurological level of the injury. Metoclopramide, a gastrointestinal prokinetic drug, has been shown to be extremely effective in normalising the impaired postprandial gastric emptying that characterises spinal cord injury.

The systemic absorption of 2 antibiotics (gentamicin and cefotiam) injected into paralysed muscle is also impaired in patients with spinal cord injury, suggesting that a decrease in therapeutic efficacy attributable to this mode of administration may be anticipated. Despite the multiplicity of drugs commonly prescribed for patients with this injury, little is known about the influence of this illness on either bioavailability or postabsorptive pharmacokinetics.

For drugs which are biotransformed and which have a relatively small volume of distribution (theophylline, lorazepam, ranitidine), single-dose intravenous pharmacokinetic profiles in patients with spinal cord injury are indistinguishable from the drug disposition profiles characteristic of healthy control populations. It may be inferred, then, that the influence of the pathophysiology of spinal cord injury on drug disposition is greatest on those drugs which are the least biotransformed and most likely to be distributed into the increased extracellular fluid volume which is characteristic of patients with this disability.

Drug disposition profiles and population pharmacokinetic models need to be defined in patients with spinal cord injury, who commonly receive a large number of medications during the acute and chronic phases of injury. In addition, the significance of the influence of the pathophysiology of the injury on such diverse areas of interest as enantioselective pharmacokinetics or the effect of altered circadian rhythms on drug disposition remains to be explored. This information is necessary to ensure that the future prescribing of medication in humans with spinal cord injury is based on an understanding of drug disposition and metabolism.

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  1. Department of Medicine and Spinal Cord Injury Service, Veterans Administration Medical Center, Long Beach, California, USA

    Jack L. Segal & Sherry R. Brunnemann

  2. Department of Medicine, University of California, Irvine, California, USA

    Jack L. Segal & Sherry R. Brunnemann

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  1. Jack L. Segal
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  2. Sherry R. Brunnemann
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Segal, J.L., Brunnemann, S.R. Clinical Pharmacokinetics in Patients with Spinal Cord Injuries. Clin-Pharmacokinet 17, 109–129 (1989). https://doi.org/10.2165/00003088-198917020-00004

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