Pharmacokinetics and toxicity of repeated oral etoposide is altered by morphine coadministration in rats.

The influence of morphine (MOR) on the pharmacokinetics and toxicity of repeated etoposide (ETP) oral administration was evaluated in rats. A decrease in the number of leukocytes in blood was observed by 5 days of treatment with ETP (30 mg/kg/day), which was prolonged by oral MOR coadministration (30 mg/kg/day). Furthermore, MOR significantly decreased animal viability.

Pharmacokinetic assessment of absorptive interaction of oral etoposide and morphine in rats.

Etoposide and morphine are well known P-glycoprotein (P-gp) substrates. The pharmacokinetic effect of morphine on plasma etoposide concentration after the oral concomitant use of etoposide and morphine in rats was assessed using a population analysis approach. A P-gp substrate quinidine and the anticholinergic drug propantheline were also administered with etoposide to compare with the effects of morphine.