Modulation effects of cyclosporine on etoposide pharmacokinetics and CNS distribution in the rat utilizing microdialysis
DE Burgio, MP Gosland, PJ McNamara - Biochemical pharmacology, 1996 - Elsevier
DE Burgio, MP Gosland, PJ McNamara
Biochemical pharmacology, 1996•ElsevierIn 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 iv 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 iv treated animals demonstrated a 53% decrease in ET
clearance. This decrease resulted in a greater than 2-fold increase in the steady-state …
etoposide (ET) under steady-state conditions and examined its extent of distribution into the
CNS of conscious animals. An iv 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 iv treated animals demonstrated a 53% decrease in ET
clearance. This decrease resulted in a greater than 2-fold increase in the steady-state …
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 (BBRcorr) 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 BBRcorr (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.
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