A study of the plasma levels of pentaerythritol mononitrate following administration of pentaerythritol tetranitrate in combination with meprobamate and diphenhydramine.

The systemic absorption of meprobamate, diphenhydramine and pentaerythritol tetranitrate (PETN) has been demonstrated following oral administration of a formulation containing all three drug substances to human volunteers. A study undertaken in dogs has also been made of the pharmacokinetics of the major nitrated metabolite of PETN when the parent drug is administered with and without meprobamate and diphenhydramine. Pentaerythritol mononitrate shows a six-fold increase in both peak plasma concentrations and area under the 0-12 hour plasma concentration-time curve when PETN is co-administered with a combination of meprobamate, diphenhydramine and nicotinic acid. No such increase is apparent when either meprobamate or diphenhydramine is excluded from the dose. Further increases in pentaerythritol mononitrate plasma levels and AUC 0-12 h are observed when all of the drugs are administered as the formulated coated tablet (VisanoCor).