Pharmaceutical Research

, Volume 11, Issue 2, pp 301–304

Improved Dose Linearity of Cyclosporine Pharmacokinetics from a Microemulsion Formulation

  • Edgar A. Mueller
  • John M. Kovarik
  • Johannes B. van Bree
  • Wolfgang Tetzloff
  • Joachim Grevel
  • Klaus Kutz
Article

DOI: 10.1023/A:1018923912135

Cite this article as:
Mueller, E.A., Kovarik, J.M., van Bree, J.B. et al. Pharm Res (1994) 11: 301. doi:10.1023/A:1018923912135

Abstract

The pharmacokinetic dose proportionality and relative bioavailability of cyclosporine from a microemulsion formulation (Sandimmune Neoral) were compared to those of the commercial formulation (Sandimmune) over the dosage range 200 to 800 mg. Single oral administrations were given as soft gelatin capsules in an open randomized study with 48 healthy volunteers. Whole-blood cyclosporine concentrations were determined by a specific monoclonal radio-immunoassay. In comparison to Sandimmune, the absorption rate (maximum concentration) and systemic availability (area under the curve) of cyclosporine were greater for Sandimmune Neoral at all dose levels investigated. The area under the curve for Sandimmune increased in a less than proportional manner with respect to dose, whereas that for Sandimmune Neoral was consistent with linear pharmacokinetics. Because of this difference, no global assessment of relative bioavailability could be performed. The relative bioavailability of cyclosporine from Sandimmune Neoral ranged from 174 to 239% compared to Sandimmune, depending on the dose level. The improvements in oral bioavailability and dose linearity of cyclosporine exposure after administration as Sandimmune Neoral should facilitate more accurate dosage titration in the clinical setting.

cyclosporine dose proportionality pharmacokinetics formulation 

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Edgar A. Mueller
    • 1
  • John M. Kovarik
    • 1
  • Johannes B. van Bree
    • 3
  • Wolfgang Tetzloff
    • 4
  • Joachim Grevel
    • 5
  • Klaus Kutz
    • 1
  1. 1.Department of Human PharmacologySandoz Pharma, Ltd.BasleSwitzerland
  2. 2.Department of Human Pharmacology, Drug SafetySandoz Pharma, Ltd.BasleSwitzerland
  3. 3.Biopharmaceutics DepartmentSandoz Pharma, Ltd.BasleSwitzerland
  4. 4.iphar CRF Institute for Clinical PharmacologyHöhenkirchen-SiegertsbrunnGermany
  5. 5.Biomedical and Agricultural Services of Texas, Inc.Austin

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