Poulsen K P, Smith G W, Davis J L, Papich M G
Department of Population Health & Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
J Vet Pharmacol Ther. 2005 Dec;28(6):539-43. doi: 10.1111/j.1365-2885.2005.00696.x.
Gastrogard, an oral formulation of omeprazole, was given to six llamas at a dose of 4 mg/kg once a day for 6 days. Plasma samples were collected at 0, 15, 30, 45, and 60 min and 2, 3, 4, 6, 8, 12, and 24 h on days 1 and 6. Plasma omeprazole concentrations were measured by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters calculated included the area under the curve (AUC(0-infinity)), peak plasma concentration (Cmax), time of peak plasma concentration (Tmax), and terminal half-life (t(1/2)). On day 6, plasma omeprazole concentrations reached a Cmax of 0.12 microg/mL at a Tmax of 45 min. The t(1/2) of omeprazole was 2.3 h and the AUC(0-infinity) was 0.38 h x microg/mL. Plasma concentrations remained above the minimum concentration for inhibition of gastric acid secretion projected from other studies on day 6 in all the llamas for approximately 6 h. However, the AUC(0-infinity) was below the concentrations associated with clinical efficacy. It was not possible to measure oral systemic bioavailability because there was no i.v. data collected from these animals. However, using data published on the i.v. pharmacokinetics of omeprazole in llamas, oral absorption was estimated to be only 2.95%. Due to low absorption the oral dose was increased to 8 and 12 mg/kg and studies were repeated. There were no significant differences in Cmax, Tmax, or AUC(0-infinity) for either of the increased doses. These results indicate that after 6 days of treatment with doses up to 12 mg/kg, oral omeprazole produced plasma drug concentrations which are not likely to be associated with clinical efficacy in camelids.
将奥美拉唑制成口服制剂胃思达,以4毫克/千克的剂量每日一次给6只美洲驼给药,持续6天。在第1天和第6天的0、15、30、45和60分钟以及2、3、4、6、8、12和24小时采集血浆样本。采用带紫外检测的高压液相色谱法测定血浆中奥美拉唑浓度。计算的药代动力学参数包括曲线下面积(AUC(0-∞))、血浆峰浓度(Cmax)、血浆峰浓度出现时间(Tmax)和末端半衰期(t(1/2))。在第6天,血浆奥美拉唑浓度在45分钟时达到Cmax为0.12微克/毫升。奥美拉唑的t(1/2)为2.3小时,AUC(0-∞)为0.38小时×微克/毫升。在第6天,所有美洲驼的血浆浓度在约6小时内均保持高于其他研究预测的抑制胃酸分泌的最低浓度。然而,AUC(0-∞)低于与临床疗效相关的浓度。由于没有从这些动物收集静脉注射数据,因此无法测量口服全身生物利用度。然而,利用已发表的美洲驼奥美拉唑静脉药代动力学数据,估计口服吸收率仅为2.95%。由于吸收低,口服剂量增加到8毫克/千克和12毫克/千克并重复研究。两种增加剂量的Cmax、Tmax或AUC((0-∞))均无显著差异。这些结果表明,以高达12毫克/千克的剂量治疗6天后,口服奥美拉唑产生的血浆药物浓度不太可能与骆驼科动物的临床疗效相关。