Application of a gamma model of absorption to oral cyclosporin

Background: Some drugs, such as cyclosporin, exhibit flat and delayed absor ption profiles, with a correlation between the delay and the peak width. Su ch profiles can be described by an absorption model in which the absorption rate is derived from a gamma distribution (of which the classical first-or der absorption model is a special case). Objective: To develop a model for the pharmacokinetics of extravascular adm inistration of cyclosporin and apply it to a study of the pharmacokinetics of cyclosporin microemulsion in stable renal transplant recipients. Patients and participants: 21 renal transplant patients receiving oral cycl osporin microemulsion 75 to 175mg twice daily. Methods: The equation of the plasma concentration-time curve after oral adm inistration was expressed as a convolution product between the absorption r ate and a multi-exponential impulse response. The convolution integral was computed analytically and expressed in terms of the incomplete gamma functi on. Cyclosporin was assayed by liquid chromatography/mass spectrophotometry . The model was fitted by nonlinear regression, using a specially developed program. Results: The gamma model yielded a good fit in all of the 21 patients studi ed. Attempts to fit the same data by a classical exponential with lag-time model failed in most patients. Conclusions: This model could simplify the Bayesian monitoring of cyclospor in therapy.