PHARMACOKINETICS AND BIOAVAILABILITY OF PENTAERITHRITYL TETRANITRATE AND 2 OF ITS METABOLITES

Two preparations containing 100 mg pentaerithrityl tetranitrate (PETN; CAS 78-11-5) each were administered to 24 healthy male volunteers in an open randomised two-way cross-over design. The test preparation was a commercially available 50 mg tablet (Pentalong(R) 50 mg Tabletten, 2 tablets per dose), the reference preparation was an aqueous suspensi on prepared immediately before application from the same 25% PETN/lact ose trituration as was used for manufacturing the tablets Blood sample s were withdrawn pre-dose and at 14 time points within 24 h after dosi ng. The resulting plasma was analysed by a GC/MS method developed on p urpose. Since in a pilot study not a single one of 120 plasma samples contained concentrations of unchanged PETN or of its metabolite pentae rithrityl trinitrate (PE-tri-N; CAS 1607-17-6) above the quantificatio n limit of 50 pg/ml, the samples of this study were assayed for the me tabolites pentaerithrityl dinitrate (PE-di-N, CAS 1607-01-8) and penta erithrityl mononitrate (PE-mono-N, CAS 1607-00-7) only. - Mean peak le vels of 17 ng/ml and 7.5 ng/ml PE-di-N were reached ca. 3 h after appl ication of tablets or trituration. The plasma elimination half-life wa s 4-5 h. Average maximum PE-mono-N levels of 79 ng/ml (tablets) and 35 ng/ml (trituration) were observed at 7 h p. appl. They declined with a half-life of 10-11 h. The relative bioavailability of the tablets as determined by means of the AUC of PE-di-N is 280-290%. This high valu e is explained by the specific properties of drug liberation and disso lution from the preparations used.