Scheidel B, Blume H, Walter K, von Nieciecki A, Babej-Dölle R M
Zentrallaboratorium Deutscher Apotheker, Eschborn, München.
Arzneimittelforschung. 1993 Nov;43(11):1211-5.
Bioavailability Study of Enteric Coated Diclofenac Formulations/1st Communication: Bioavailability study following single-dose administration of a multiple-unit formulation compared with a single-unit formulation Relative bioavailability of diclofenac (CAS 15307-86-5) was investigated after single-dose administration of an enteric coated multiple-unit formulation (Diclo-Puren 50, test) in comparison to a single-unit dosage form (reference). The study was carried out in a three-way changeover design with a group of 18 healthy male volunteers. Diclofenac plasma concentrations were measured using a selective and sensitive GLC-MS method after liquid-liquid extraction and subsequent derivatisation. Area under the curve (AUC) and maximum plasma concentrations (Cmax) were evaluated as pharmacokinetic characteristics. Moreover, time of maximum plasma concentration (tmax), lag-time (tlag) and plateau time of concentrations above minimum effective concentrations (MEC) of 50 ng/ml (tMEC(50)) and 100 ng/ml (tMEC(100)), respectively were calculated. Bioequivalence concerning AUC and Cmax was assessed by calculating 90%-confidence intervals using parametric (ANOVA, ANOVAlog) and non-parametric (Mann-Whitney) methods. Due to the inclusion rule bioequivalence was accepted if one of the calculated intervals was completely in the range of 80 to 125% (AUC) and 70 to 143% (Cmax). tmax, tlag and tMEC were evaluated considering the differences of mean values. Individual plasma profiles of diclofenac are more homogeneous after administration of the test formulation than after administration of the reference product. Mean relative bioavailability of the test formulation was calculated as 99%. Maximum plasma concentrations (mean +/- SD) were determined as 1159 +/- 632 ng/ml (test) and as 1481 +/- 637 ng/ml (reference). Maximum plasma concentrations (mean +/- SD) occurred 1.4 +/- 0.7 h (test) and 1.8 +/- 0.7 h (reference) after administration.(ABSTRACT TRUNCATED AT 250 WORDS)
肠溶包衣双氯芬酸制剂的生物利用度研究/首次通讯：多单元制剂与单单元制剂单剂量给药后的生物利用度研究 与单单元剂型（参比制剂）相比，研究了单剂量给予肠溶包衣多单元制剂（双氯芬酸普伦50，受试制剂）后双氯芬酸（CAS 15307-86-5）的相对生物利用度。该研究采用三交叉设计，纳入18名健康男性志愿者。采用选择性灵敏的气相色谱-质谱法，经液-液萃取及后续衍生化后测定双氯芬酸血浆浓度。以曲线下面积（AUC）和最大血浆浓度（Cmax）作为药代动力学特征进行评价。此外，分别计算了最大血浆浓度出现时间（tmax）、滞后时间（tlag）以及浓度高于50 ng/ml（tMEC(50)）和100 ng/ml（tMEC(100)）的最低有效浓度（MEC）时的平台期时间。采用参数法（方差分析、对数方差分析）和非参数法（曼-惠特尼检验）计算90%置信区间，评估AUC和Cmax的生物等效性。根据纳入规则，若计算得到的区间之一完全在80%至125%（AUC）和70%至143%（Cmax）范围内，则接受生物等效性。考虑均值差异对tmax、tlag和tMEC进行评价。与给予参比制剂后相比，给予受试制剂后双氯芬酸的个体血浆浓度曲线更为均匀。受试制剂的平均相对生物利用度计算为99%。最大血浆浓度（均值±标准差）分别为1159±632 ng/ml（受试制剂）和1481±637 ng/ml（参比制剂）。给药后最大血浆浓度（均值±标准差）出现时间分别为1.4±0.7小时（受试制剂）和1.8±0.7小时（参比制剂）。（摘要截选至250词）
