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Clinical Pharmacokinetics

, Volume 40, Issue 5, pp 375–382 | Cite as

Application of a Gamma Model of Absorption to Oral Cyclosporin

  • Jean DebordEmail author
  • Eléonore Risco
  • Michel Harel
  • Yannick Le Meur
  • Mathias Büchler
  • Gérard Lachâtre
  • Chantal Le Guellec
  • Pierre Marquet
Original Research Article

Abstract

Background: 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).

Objective: 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.

Patients and participants: 21 renal transplant patients receiving oral cyclosporin microemulsion 75 to 175mg twice daily.

Methods: 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.

Results: 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.

Conclusions: This model could simplify the Bayesian monitoring of cyclosporin therapy.

Keywords

Cyclosporin Incomplete Gamma Function Gamma Model Oral Cyclosporin Cyclosporin Microemulsion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This study was supported in part by the University Hospital of Limoges, France. We are indebted to Drs J. Gobburu and M. Weiss for providing some bibliographic references.

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Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Jean Debord
    • 1
    Email author
  • Eléonore Risco
    • 1
  • Michel Harel
    • 2
  • Yannick Le Meur
    • 3
  • Mathias Büchler
    • 3
  • Gérard Lachâtre
    • 1
  • Chantal Le Guellec
    • 4
  • Pierre Marquet
    • 5
  1. 1.Service de Pharmacologie-ToxicologieHôpital DupuytrenLimogesFrance
  2. 2.Institut Universitaire de Formation des MaîtresLimogesFrance
  3. 3.Service de NéphrologieHôpital DupuytrenLimogesFrance
  4. 4.Service de PharmacologieCHU BretonneauToursFrance
  5. 5.Service de NéphrologieCHU BretonneauToursFrance

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