Schulz H U, Düsing R, Grunwald F, Czaja J, Lührmann B, Frecks H J
Medical University Lübeck, Department of Angiology and Geriatric, Germany.
Int J Clin Pharmacol Ther Toxicol. 1992 Apr;30(4):139-44.
A bioavailability study with three test batches of a sustained release formulation of carbamazepine, which differed only in their in vitro dissolution profiles, was performed in 18 healthy subjects to compare the respective plasma concentration profiles and to determine the relative bioavailability of carbamazepine (CBZ). This investigation was designed to examine the extent to which these differences in dissolution properties can be determined from the results of in vivo tests. The randomized, single-dose, crossover study comprised three experimental periods, separated by washout intervals of three weeks' duration. A sensitive, validated HPLC method was used for the analysis of serum carbamazepine concentrations. Bioequivalence was only accepted if the 90% confidence interval (parametric or nonparametric) for the quotients of the mean values of the variables for each test and reference preparation was completely within the bioequivalence range. For this calculation, all three test preparations were compared with one another. The following relative bioavailability values were obtained: A/B: AUC = 87% (83%, 92%), MRT = 106% (103%, 109%), HVD = 109% (105%, 113%). C/B: AUC = 106% (101%, 110%), MRT = 98% (96%, 99%), HVD = 87% (82%, 91%). C/A: AUC = 124% (117%, 130%), MRT = 92% (89%, 94%), HVD = 79% (74%, 84%). There was a positive correlation between the in vitro dissolution rates of the different test batches and the respective degree of carbamazepine absorption as determined in vivo, while an inverse correlation existed between the in vitro dissolution rates on one side and the mean residence time (MRT) as well as the half value duration (HVD) on the other.(ABSTRACT TRUNCATED AT 250 WORDS)
对卡马西平缓释制剂的三个测试批次进行了生物利用度研究，这三个批次仅在体外溶出曲线方面存在差异。研究在18名健康受试者中开展，以比较各自的血浆浓度曲线，并确定卡马西平（CBZ）的相对生物利用度。本研究旨在考察从体内试验结果中能够在多大程度上确定这些溶出特性的差异。该随机、单剂量、交叉研究包括三个实验期，中间间隔为期三周的洗脱期。采用一种灵敏且经验证的高效液相色谱法分析血清中卡马西平的浓度。只有当每个测试制剂和参比制剂变量均值商的90%置信区间（参数法或非参数法）完全在生物等效性范围内时，才接受生物等效性。为进行此计算，将所有三个测试制剂相互比较。获得了以下相对生物利用度值：A/B：AUC = 87%（83%，92%），MRT = 106%（103%，109%），HVD = 109%（105%，113%）。C/B：AUC = 106%（101%，110%），MRT = 98%（96%，99%），HVD = 87%（82%，91%）。C/A：AUC = 124%（117%，130%），MRT = 92%（89%，94%），HVD = 79%（74%，84%）。不同测试批次的体外溶出速率与体内测定的卡马西平吸收程度之间存在正相关，而体外溶出速率与平均驻留时间（MRT）以及半衰期（HVD）之间存在负相关。（摘要截短于250词）
