国产盐酸曲马多栓的人体药代动力学和相对生物利用度研究

The Pharmacokinetics and Relative Bioavailability of Tramadol Hydrochloride Suppositories in Healthy Volunteers

随机交叉直肠给予１２名健康男性受试者１００ ｍｍ进口和国产盐酸曲马多栓。采用气相色谱法测定给药后同时间的血浆药物浓度，研究国产盐酸曲马多栓在人体内的药代动力学和相对生物利用度。研究结果表明：进口和国产盐酸曲马多栓的药代动力学参数（均数±标准差）：Ｔｍａｘ分别为２．６±１．０和２．７±１．１ｈ；Ｃｍａｘ分别为３８４± ６７和３９２± ７１ｕ ｇ·Ｌ－１； Ｔ１／２分别为８．７± ２．５和８．９± ２．６ ｈ； Ｖｄ／Ｆ分别为 ４．２±１．２和 ４．４±１．３ Ｌ· ｋｇ－１； ＣＬ／Ｆ分别为 ２２．８± １０．９和 ２２．８ ±９．２ Ｌ· ｈ－１；ＡＵＣ０－４８分别为４７９２± １５７６和４７１９ ± １５８９ ｕ ｇ·ｈ·Ｌ－１。经配对ｔ检验上述参数差异均无显著性意义。国产盐酸曲马多栓相对生物利用度Ｆ为９８％±１０％；其９０％的可信区间为９３％－１１３％。结果提示国产盐酸曲马多栓和进口盐酸曲马多栓具有生物等效性。

The pharmacokinetics and relative bioavailability of domestic tramadol hydrochloride in suppositories after rectal administration were determined in a balance cross over study in 12 healthy male volunteers in comparison with imported tramadol hydrochloride in suppositories. Each volunteer received two single doses (l00 mg) tramadol hydrochloride in suppository, one domestic and one imported. The tramadol in plasma was detected by GC. The pharmacokinetic parameters of imported and domestic tramadol hydrochloride in suppositories were as followings (mean ± SD): Tmax. was 2.6 ± l.0 h and 2.7 ± l.l h, the Cmax was 384 ± 67μg' L-1 and 392 ± 71 μ g ·L-1, terminal half-life time (T1/2) was 8.7 ± 2.5 h and 8.9 ± 2.6 h, VM was 4.2 ± l.2 L· kg-l and 4.4 ± l.3 L kg-1, CL/F was 22.8 ± 10.9 L h-land 22.8 ± 9.2 L h-1, and AUC0-48, was 4792 ± 1576 μ g· h· L-1 and 4719 ± 1589μg·h· L-1, respectively. All the parameters were not different with statistics significance examined by paired t-test (P> 0.05). The extent of relative bioavailability (F) of domestic tramadol hydrochloride in soppositories, based on the AUC0-48,, data, was 98% (10%, with a 90% confidence interval of 93% ~ 13%. The results show that the two products are bioequivalent.