Pharmacokinetics and bioavailability of pentaerithrityl tetranitrate and two of its metabolites.
Two preparations containing 100 mg pentaerithyrityl 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 50 mg Tabletten, 2 tablets per dose), the reference preparation was an aqueous suspension prepared immediately before application from the same 25% PETN/lactose trituration as was used for manufacturing the tablets. Blood samples were withdrawn pre-dose and at 14 time points within 24 h after dosing. The resulting plasma was analysed by a GC/MS method developed on purpose. Since in a pilot study not a single one of 120 plasma samples contained concentrations of unchanged PETN or of its metabolite pentaerithrityl trinitrate (PE-tri-N, CAS 1607-17-6) above the quantification limit of 50 pg/ml, the samples of this study were assayed for the metabolites pentaerithrityl dinitrate (PE-di-N, CAS 1607-01-8) and pentaerithrityl mononitrate (PE-mono-N, CAS 1607-00-7) only. -Mean peak levels of 17 ng/ml and 7.5 ng/ml PE-di-N were reached ca. 3 h after application of tablets or trituration. The plasma elimination half-life was 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 value is explained by the specific properties of drug liberation and dissolution from the preparations used.
Weber
W
W
L.A.B. Gesellschaft für pharmakologische Untersuchungen mbH & Co., Neu-Ulm, Germany.
Michaelis
K
K
Luckow
V
V
Kuntze
U
U
Stalleicken
D
D
D000328:Adult; D001682:Biological Availability; D001711:Biotransformation; D018592:Cross-Over Studies; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D008297:Male; D010417:Pentaerythritol Tetranitrate / Q000031:analogs & derivatives*; D011409:Propylene Glycols / Q000493:pharmacokinetics*; D014665:Vasodilator Agents / Q000493:pharmacokinetics*
D011409:Propylene Glycols; D014665:Vasodilator Agents; D010417:Pentaerythritol Tetranitrate; C100210:pentrinitrol