Scheidel B, Blume H, Stenzhorn G, Siewert M, Babej-Dölle R M
Zentrallaboratorium Deutscher Apotheker, Eschborn.
Arzneimittelforschung. 1991 Mar;41(3):212-8.
Assessment of Bioavailability of Organic Nitrates/Comparative bioavailability study of sustained-release isosorbide dinitrate preparations. Relative bioavailabilities of isosorbide dinitrate (ISDN, CAS 87-33-2) and the metabolite isosorbide-5-mononitrate (IS-5-MN, CAS 16051-77-7) were studied after application of Maycor retard 40 (sustained-release capsules, multiple unit formulation, test preparation) in comparison to sustained-release tablets (single unit formulation, reference preparation) with 16 healthy male volunteers in a two-way crossover design. Test and reference formulations were previously characterised in vitro by dissolution tests. ISDN, IS-5-MN (IS-2-MN) plasma concentrations were determined using a selective and sensitive GLC-method with ECD-detection. As pharmacokinetic parameters AUC, Cmax and half value duration (HVD) were evaluated. Bioequivalence was assessed by calculating 90%-confidence intervals (ANOVA, ANOVAlog, Mann-Whitney-test) for ISDN and IS-5-MN. Bioequivalence was accepted if due to the inclusion rule one of the calculated intervals fulfill the requirements of 80 and 120% (AUC) or 70 and 130% (Cmax, HVD), respectively. Relative bioavailability of the test formulation was calculated as 94% (ISDN) and 96% (IS-5-MN). Maximum plasma concentrations of ISDN (IS-5-MN) were determined for the test preparation as 14.3 +/- 3.1 ng/ml (265 +/- 45 45 ng/ml) and as 22.8 +/- 12.6 ng/ml (287 +/- 59 ng/ml) for the reference product. HVD-values were for the test preparation 4.5 +/- 1.3 h (ISDN) and 8.5 +/- 1.3 h (IS-5-MN) and for the reference formulation 3.1 +/- 1.2 h (ISDN) and 8.1 +/- 1.4 (IS-5-MN).(ABSTRACT TRUNCATED AT 250 WORDS)
有机硝酸盐的生物利用度评估/缓释硝酸异山梨酯制剂的比较生物利用度研究。在16名健康男性志愿者中，采用双向交叉设计，比较了Maycor retard 40（缓释胶囊，多单元制剂，试验制剂）与缓释片（单单元制剂，参比制剂）应用后硝酸异山梨酯（ISDN，CAS 87-33-2）及其代谢产物5-单硝酸异山梨酯（IS-5-MN，CAS 16051-77-7）的相对生物利用度。试验制剂和参比制剂先前已通过溶出度试验进行体外表征。采用具有电子捕获检测的选择性灵敏气相色谱法测定ISDN、IS-5-MN（IS-2-MN）的血浆浓度。评估药代动力学参数AUC、Cmax和半衰期（HVD）。通过计算ISDN和IS-5-MN的90%置信区间（方差分析、对数方差分析、曼-惠特尼检验）评估生物等效性。如果根据纳入规则，计算出的区间之一分别满足80%至120%（AUC）或70%至130%（Cmax、HVD）的要求，则接受生物等效性。试验制剂的相对生物利用度计算为94%（ISDN）和96%（IS-5-MN）。试验制剂的ISDN（IS-5-MN）最大血浆浓度测定为14.3±3.1 ng/ml（265±45 ng/ml），参比制剂为22.8±12.6 ng/ml（287±59 ng/ml）。试验制剂的HVD值为4.5±1.3小时（ISDN）和8.5±1.3小时（IS-5-MN），参比制剂为3.1±1.2小时（ISDN）和8.1±1.4小时（IS-5-MN）。（摘要截断于250字）
