ATOVAQUONE HAS NO EFFECT ON THE PHARMACOKINETICS OF PHENYTOIN IN HEALTHY MALE-VOLUNTEERS

The potential pharmacokinetic interaction between atovaquone and pheny toin was investigated in 12 healthy male volunteers. Each volunteer re ceived a single 600 mg oral dose of phenytoin in the two treatment per iods. On one occasion phenytoin was taken alone and on the other after pre-treatment with 2000 mg atovaquone taken as two doses of 1000 mg a s a microfluidized suspension. The mean (+/-s.d) peak plasma concentra tions (C-max), apparent total clearance (CL/F) and terminal half-life (t(1/2)) for phenytoin when administered alone were 10.6 (1.8) mg l(-1 ), 24.3 (7.7) ml min(-1) and 25 (8) h, respectively. When administered together with atovaquone, phenytoin C-max, CL/F and t(1/2,z) were 10. 9 (2.0) mg l(-1), 23.8 ml min(-1) and 24 (6) h, respectively. There we re no statistically significant differences in any of these plasma pha rmacokinetic parameters. There were also no statistically significant differences in the fraction of circulating drug not bound to plasma pr otein or urinary excretion of 5-hydroxyphenyl-phenyl-hydantoin. In con clusion, there was no effect of atovaquone on the pharmacokinetics of phenytoin or its major metabolite after a single dose.