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Modulation effects of cyclosporine on etoposide pharmacokinetics and CNS distribution in the rat utilizing microdialysis.

Abstract：

:In the present study, we evaluated the pharmacokinetics of the chemotherapeutic agent etoposide (ET) under steady-state conditions and examined its extent of distribution into the CNS of conscious animals. An i.v. infusion of 15 mg/kg/hr was administered to nine rats. Each of the nine rats also received the potent multidrug resistance (MDR) modulator cyclosporine (CSA). Upon the addition of CSA, the i.v. treated animals demonstrated a 53% decrease in ET clearance. This decrease resulted in a greater than 2-fold increase in the steady-state concentrations of ET> The corrected brain-blood ratio (BBR (corr)) was 0.36 +/- 0.18 prior to CSA treatment, and although CNS concentrations increased upon the addition of CSA, there was no increase in the BBR(corr) (0.24 +/- 0.10). The present study demonstrates that the increase of ET in the CNS following CSA is a result of a decrease in ET systemic clearance and not an inhibition of ET efflux from the CNS.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Burgio DE,Gosland MP,McNamara PJ

doi

10.1016/0006-2952(95)02437-9

subject

Has Abstract

pub_date

1996-04-12 00:00:00

pages

987-92

issue

7

eissn

0006-2952

issn

1873-2968

pii

0006-2952(95)02437-9

journal_volume

51

pub_type

杂志文章

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