Bioavailability and Pharmacokinetic Profile of Glyceryl Trinitrate and of Glyceryl Dinitrates during Application of a New Glyceryl Trinitrate Transdermal Patch
| Autor: | Henry Caplain, Antonino Santoro, Ivo Setnikar, Lucio C. Rovati, Virginie Gualano |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Vasodilator Agents Metabolite Cmax Biological Availability Absorption (skin) Pharmacology Administration Cutaneous Nitroglycerin chemistry.chemical_compound Pharmacokinetics Drug Discovery Humans Distribution (pharmacology) Cross-Over Studies Chemistry Headache Adhesiveness Half-life Nausea Crossover study Bioavailability Therapeutic Equivalency Area Under Curve Half-Life |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1616-7066 0004-4172 |
| DOI: | 10.1055/s-0031-1300289 |
| Popis: | The pharmacokinetics and bioavailability of glyceryl trinitrate (GTN, CAS 55-63-0) and of its main metabolites, i.e. 1,2-glyceryl dinitrate (1,2-GDN, CAS 621-65-8) and 1,3-glyceryl dinitrate (1,3-GDN, CAS 623-87-0), were compared during a single 24-h application of a new GTN transdermal patch (Epinitril 10, hereinafter called EPI-10) or a reference patch (hereinafter called ND-10) releasing 10 mg GTN in 24 h. The study was an open, randomized balanced cross-over study on 24 healthy male volunteers to whom the patches were applied to the antero-lateral part of the thorax in two periods separated by a 3-day wash-out. Blood samples were collected before administration, during the 24-h patch application and at 0.5, 2 and 3 h after patch removal. Assayed in plasma were GTN, 1,2-GDN and 1,3-GDN using validated GC/MS methods with stable isotope-labeled internal standards (15N3-GTN, 15N2-1,2-GDN, and 15N2-1,3-GDN). The ratios of the AUCs of GTN, 1,2-GDN and 1,3-GDN measured during application of EPI-10 or of ND-10 were within the 0.85-1.25 limits required to assess equivalence of the extent of bioavailability. The ratios of the Cmax were within said limits for the signal metabolite 1,2-GDN and only slightly below (0.78-1.16) for the parent GTN. EPI-10 can therefore be considered equivalent to ND-10 also with regard to the rate of bioavailability. Under both patches GTN reached steady-state levels after 3-6 h of patch application and remained on sustained levels during the whole 24-h application. The plasma levels of 1,2-GDN were about 6 times higher than those of GTN. The plasma levels of 1,3-GDN were similar to those of GTN. Upon removal of the patches the concentrations of the three nitrates fell to negligible values within 3 h. Both patches were well tolerated at the application site. For its small size, thinness and transparency, EPI-10 is very patient friendly, a quality that improves compliance with the therapeutic regimen. |
| Databáze: | OpenAIRE |
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