当前位置： SCI文献检索 > JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > Differential influence of two cyclosporine formulations on everolimus pharmacokinetics: a clinically relevant pharmacokinetic interaction.

Differential influence of two cyclosporine formulations on everolimus pharmacokinetics: a clinically relevant pharmacokinetic interaction.

Abstract：

:Everolimus is an immunosuppressant intended for use with cyclosporine in acute-rejection prophylaxis following organ transplantation. The possibility of a drug interaction of cyclosporine on everolimus was assessed. In this randomized, two-period, crossover study, 24 healthy subjects received a single oral dose of 2 mg everolimus alone and with one of two cyclosporine formulations: either 175 mg Neoral or 300 mg Sandimmune. The single doses of Neoral and Sandimmune were chosen to yield similar average areas under the concentration-time curve (AUC). Treatments were separated by a 14-day washout period. Cyclosporine AUCs were similar for both formulations (p = 0.53), whereas the peak concentration (Cmax) was significantly higher for Neoral (p = 0.02). Simultaneous administration of Neoral with everolimus increased everolimus Cmax and AUC by 82% and 168%, respectively (p = 0.0001). Coadministration of Sandimmune with everolimus did not affect everolimus Cmax (p = 0.59) but increased everolimus AUC by 74% on average (p = 0.0001). Everolimus elimination half-lives were unchanged in the presence of both cyclosporine formulations. The everolimus AUC increase with Neoral coadministration was significantly greater than the AUC increase with Sandimmune (p = 0.008). However, there was no apparent association between cyclosporine Cmax and the change in everolimus AUC with cyclosporine coadministration. If Neoral or Sandimmune is removed from an everolimus-cyclosporine immunosuppressive regimen, a two- to three-fold decrease in everolimus exposure is expected. Therapeutic monitoring of everolimus concentrations would be helpful after the removal of cyclosporine to individually titrate everolimus exposure.

journal_name

J Clin Pharmacol

journal_title

Journal of clinical pharmacology

authors

Kovarik JM,Kalbag J,Figueiredo J,Rouilly M,Frazier OL,Rordorf C

doi

10.1177/0091270002042001011

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

95-9

issue

eissn

0091-2700

issn

1552-4604

journal_volume

pub_type

临床试验,杂志文章,随机对照试验

在线工具

Differential influence of two cyclosporine formulations on everolimus pharmacokinetics: a clinically relevant pharmacokinetic interaction.