Atovaquone has no effect on the pharmacokinetics of phenytoin in healthy male volunteers

The potential pharmacokinetic interaction between atovaquone and phenytoin was investigated in 12 healthy male volunteers. Each volunteer received a single 600  mg oral dose of phenytoin in the two treatment periods. 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 as a microfluidized suspension. The mean (±s.d.) peak plasma concentrations ( C _max), apparent total clearance (CL/ F ) and terminal half-life ( t _½) 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 _½,z were 10.9 (2.0)  mg l⁻¹, 23.8  ml min⁻¹ and 24(6)  h, respectively. There were no statistically significant differences in any of these plasma pharmacokinetic parameters. There were also no statistically significant differences in the fraction of circulating drug not bound to plasma protein or urinary excretion of 5-hydroxyphenyl-phenyl-hydantoin. In conclusion, there was no effect of atovaquone on the pharmacokinetics of phenytoin or its major metabolite after a single dose.