罗红霉素片剂生物利用度的比较研究

COMPARISON OF ROXITHROMYCIN BIOAVAILABILITY OF A CONVENTIONAL AND A DISPERSIBLE TABLET FORMULATION

为比较不同剂型罗红霉素的生物利用度，用微生物管碟检定法（藤黄微球菌ＣＭＣＣ（Ｂ）２８００１）测定了１０名男性健康受试者口服罗红霉素分散片（制剂Ａ）和罗红霉素片（制剂Ｂ）后不同时间血浆中活性药物的浓度，绘制了血药浓度—时间曲线。结果表明，受试者交叉口服含罗红霉素１５０ｍｇ的制剂Ａ和制剂Ｂ后，血浆Ｔｍａｘ分别为１７±０９和３７±１６ｈ，Ｃｍａｘ分别为４９７±１１７和２０４±１２６μｇ·ｍｌ－１，ＡＵＣ０→∞分别为６２２±１１９和３５０±１６９μｇ·ｈ·ｍｌ－１。以制剂Ａ为参比，制剂Ｂ中罗红霉素的相对生物利用度仅为５９８％±３２６％，两种制剂的药物吸收程度有显著差异（Ｐ＜００１）。初步分析提示。

Following oral administrations of a single dose of 150 mg roxithromycin dispersible tablet (formulation A, a new formulation for clinical trial) and conventional tablet (formulation B, purchased from the market) to each of 10 healthy male volunteers in a randomized crossover design, the plasma levels of active drug at different times were determined by a microbial assay with Micrococcus luteus CMCC (B) 28001 and the plasma concentration—time profiles were obtained. The T_(max) values of formulation A and B obtained were 1.7±0.9 and 3.7±1.6 h, the C_(max) values were 4.97±1.17 and 204±1.26 μg·ml-1 and the AUC0→∞ values were 62.2±11.9 and 35.0±16.9 μg·h·ml^(-1), respectively. Surprisingly, the relative bioavailability of formulation B was found to be only 59.8%±32.6% (P<0.01). The low bioavailability of the latter formulation was attributed to poor release of roxithromycin in the gastric site, which was proposed as a key factor to influence drug absorption. Other related factors were also discussed.