Pieters F A, Zuidema J
Int J Clin Pharmacol Ther Toxicol. 1987 Jul;25(7):396-400.
The absolute oral bioavailability of dapsone (DDS) was established in dogs and healthy volunteers by comparing AUC's after oral and intravenous administration. Five female inbred beagles each received 100 mg DDS orally and intravenously as a bolus injection in a randomized cross-over study. DDS serum concentrations were determined using HPLC. After both routes of administration, linear pharmacokinetics were observed, the elimination half-life (t1/2) amounting between 5.8 and 10.2 h. After oral administration, AUC values between 56.1 and 99.2 mg X h X l-1 were found, while after intravenous administration AUC's were between 63.5 and 98.1 mg X h X l-1. The absolute oral bioavailability, corrected for differences in t1/2, averaged 107 +/- 9% (SD). A similar study was carried out in 2 female and 3 male healthy volunteers. The intravenous dose was reduced to 50 mg and given as an infusion. Pharmacokinetics were linear after both routes of administration. The t1/2 values amounted between 15.6 and 30.4 h. AUC's ranged from 24.0 to 75.4 mg X h X l-1 after oral administration and from 13.3 to 37.5 mg X h X l-1 after intravenous infusion of half of the oral dose. The absolute, t1/2-corrected oral bioavailability was calculated to be 86 to 104%. Complete bioavailability of DDS was demonstrated in dogs and healthy volunteers. The method used in this study might help to detect possible DDS malabsorption in leprosy and dermatitis herpetiformis patients.
通过比较口服和静脉给药后的药时曲线下面积(AUC),在犬和健康志愿者中确定了氨苯砜(DDS)的绝对口服生物利用度。在一项随机交叉研究中,5只雌性近交比格犬每只均接受了100mg DDS的口服和静脉推注。使用高效液相色谱法(HPLC)测定DDS血清浓度。两种给药途径后均观察到线性药代动力学,消除半衰期(t1/2)在5.8至10.2小时之间。口服给药后,AUC值在56.1至99.2mg·h·L-1之间,而静脉给药后AUC值在63.5至98.1mg·h·L-1之间。经t1/2差异校正后的绝对口服生物利用度平均为107±9%(标准差)。在2名女性和3名男性健康志愿者中进行了类似研究。静脉剂量降至50mg并作为静脉滴注给药。两种给药途径后药代动力学均呈线性。t1/2值在15.6至30.4小时之间。口服给药后AUC范围为24.0至75.4mg·h·L-1,静脉滴注口服剂量的一半后AUC范围为13.3至37.5mg·h·L-1。经t1/2校正后的绝对口服生物利用度计算为86%至104%。在犬和健康志愿者中证实了DDS的完全生物利用度。本研究中使用的方法可能有助于检测麻风病和疱疹样皮炎患者中可能存在的DDS吸收不良情况。