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Clin Pharmacokinet. 2001;40(5):375-82.

Application of a gamma model of absorption to oral cyclosporin.

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Service de Pharmacologie-Toxicologie, Hĵpital Dupuytren, Limoges, France.



Some drugs, such as cyclosporin, exhibit flat and delayed absorption profiles, with a correlation between the delay and the peak width. Such profiles can be described by an absorption model in which the absorption rate is derived from a gamma distribution (of which the classical first-order absorption model is a special case).


To develop a model for the pharmacokinetics of extravascular administration of cyclosporin and apply it to a study of the pharmacokinetics of cyclosporin microemulsion in stable renal transplant recipients.


21 renal transplant patients receiving oral cyclosporin microemulsion 75 to 175 mg twice daily.


The equation of the plasma concentration-time curve after oral administration was expressed as a convolution product between the absorption rate and a multi-exponential impulse response. The convolution integral was computed analytically and expressed in terms of the incomplete gamma function. Cyclosporin was assayed by liquid chromatography/mass spectrophotometry. The model was fitted by nonlinear regression, using a specially developed program.


The gamma model yielded a good fit in all of the 21 patients studied. Attempts to fit the same data by a classical exponential with lag-time model failed in most patients.


This model could simplify the Bayesian monitoring of cyclosporin therapy.

[Indexed for MEDLINE]

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