A Bayesian Kinetic Control Strategy for Cyclosporin in Renal Transplantation
Although cyclosporin has brought about a dramatic improvement in graft survival after transplantation, its use in this therapeutic setting may be associated with considerable control problems. Many clinically oriented studies have shown remarkable fluctuations in cyclosporin blood concentrations and this has presented a challenge primarily to those interested in pharmacokinetics. This presupposes, of course, that the fluctuations are in large part due to pharmacokinetic variability of one sort or another. There may well be other reasons. An excellent overview of the topic — including suggestions for one pharmacokinetic strategy — has been provided recently by Kahan and Grevel . In response to the often quoted and observed wide range of cyclosporin concentrations, these authors stress that a dosing strategy that achieves uniform drug levels by compensating for pharmacokinetic variability is essential for the promotion of rational cyclosporin regimens. While their comments were directed at renal transplantation, there is no doubt that such comments are equally applicable to the use of cyclosporin in other transplant situations.
KeywordsRenal Transplantation Compartment Model Pharmacokinetic Variability Cyclosporin Concentration Friedman ANOVA
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- 2.A. A. Niven, J. Grevel, M. Al-Banna, A. W. Kelman, B. Whiting, and J. D. Briggs. Pharma-cokinetics of cyclosporin in the early post-operative period following renal transplantation. Brit. J. Clin. Pharmaco. 26:626 (1988).Google Scholar
- 3.B. Whiting, A. A. Niven, A. W. Kelman, and J. D. Briggs. Improved therapeutic control of cyclosporin in renal transplantation. Decision Support for Patient Management: Measurement, Modeling and Control, British Medical Informatics Society, London, 1989, pp. 33–38.Google Scholar
- 4.A. A. Niven. The control of cyclosporin in transplantation: Pharmacokinetic aspects. Doctoral Thesis, University of Glasgow, 1990.Google Scholar
- 6.S. L. Beal and L. B. Sheiner. NONMEM User’s Guides, I–VI. University of California, San Francisco, 1979–1989.Google Scholar