Common antimalarial drugs do not affect metabolism of diazepam and desmethyldiazepam by human liver microsomes in-vitro

We have investigated the effect of various antimalarial compounds on the metabolism of diazepam and nordiazepam in-vitro by human liver microsomes. Production of nordiazepam and C₃-hydroxydiazepam (temazepam) from diazepam, and C₃-hydroxynordiazepam (oxazepam) from nordiazepam was not saturable within the range of substrate concentrations used (5-500 μM diazepam, 5-200 μM nordiazepam). At a fixed low diazepam concentration (20 μM), none of the antimalarial drugs tested had statistically significant effects on the metabolism of diazepam to nordiazepam and temazepam. Similarly, at nordiazepam 140 μM, none of the antimalarial drugs tested had statistically significant effects on the metabolism of nordiazepam to oxazepam. We conclude that in-vivo, none of the antimalarials investigated are likely to have a clinically significant effect on the metabolism of diazepam or nordiazepam.