Pharmacokinetics of an everolimus-cyclosporine immunosuppressive regimen over the first 6 months after kidney transplantation

John M. Kovarik, Bruce Kaplan, Hélio Tedesco Silva, Barry D. Kahan, Jacques Dantal, Louis McMahon, Stephane Berthier, Chyi Hung Hsu, Christiane Rordorf

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The pharmacokinetics of everolimus were characterized over the first 6 months post transplant in 731 patients receiving either 0.75 or 1.5 mg bid everolimus in addition to cyclosporine and corticosteroids. Pharmacokinetic data consisted of 4014 everolimus trough concentrations (Cmin) obtained in all patients and 659 area under the concentration-time curve (AUC) -profiles obtained at months 2, 3, and 6 in a subset of 261 patients. Cmins averaged 4.3 ± 2.4 and 7.2 ± 4.2 ng/mL at 0.75 and 1.5 mg bid, indicating a 20% under-proportionality at the upper dose level. Cmins were 19-34% lower in the first month compared with months 2 through 6-values. AUC was dose-proportional and stable over time, averaging 77 ± 32 and 136 ± 57 ng.h.mL-1 at the two dose levels. Within- and between-patient variability in AUC were 27% and 31%, respectively. There was no influence of sex, age (16-66 years), or weight (42-132 kg) on AUC. Everolimus exposure was significantly lower by an average 20% in blacks. Everolimus exposure was relatively stable over the first 6 months post transplant, with no major departure from dose-proportionality over the therapeutic dose range. Weight-adjusted dosing (mg/ kg) does not appear warranted. Black patients may have lower bioavailability and/or higher clearance of everolimus compared with white patients.

Original languageEnglish (US)
Pages (from-to)606-613
Number of pages8
JournalAmerican Journal of Transplantation
Volume3
Issue number5
DOIs
StatePublished - May 2003
Externally publishedYes

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Immunosuppressive Agents
Kidney Transplantation
Cyclosporine
Pharmacokinetics
Transplants
Weights and Measures
Biological Availability
Everolimus
Adrenal Cortex Hormones

Keywords

  • Cyclosporine
  • Everolimus
  • Immunosuppressants
  • Pharmacokinetics

ASJC Scopus subject areas

  • Immunology

Cite this

Pharmacokinetics of an everolimus-cyclosporine immunosuppressive regimen over the first 6 months after kidney transplantation. / Kovarik, John M.; Kaplan, Bruce; Tedesco Silva, Hélio; Kahan, Barry D.; Dantal, Jacques; McMahon, Louis; Berthier, Stephane; Hsu, Chyi Hung; Rordorf, Christiane.

In: American Journal of Transplantation, Vol. 3, No. 5, 05.2003, p. 606-613.

Research output: Contribution to journalArticle

Kovarik, JM, Kaplan, B, Tedesco Silva, H, Kahan, BD, Dantal, J, McMahon, L, Berthier, S, Hsu, CH & Rordorf, C 2003, 'Pharmacokinetics of an everolimus-cyclosporine immunosuppressive regimen over the first 6 months after kidney transplantation', American Journal of Transplantation, vol. 3, no. 5, pp. 606-613. https://doi.org/10.1034/j.1600-6143.2003.00107.x
Kovarik, John M. ; Kaplan, Bruce ; Tedesco Silva, Hélio ; Kahan, Barry D. ; Dantal, Jacques ; McMahon, Louis ; Berthier, Stephane ; Hsu, Chyi Hung ; Rordorf, Christiane. / Pharmacokinetics of an everolimus-cyclosporine immunosuppressive regimen over the first 6 months after kidney transplantation. In: American Journal of Transplantation. 2003 ; Vol. 3, No. 5. pp. 606-613.
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AU - Dantal, Jacques

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