Itokazu Gail S, Fischer James H, Manitpisitkul Prasarn, Hariharan Radhika, Danziger Larry H
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, USA.
Pharmacotherapy. 2002 Nov;22(11):1420-5. doi: 10.1592/phco.22.16.1420.33698.
To investigate the effect of histamine2 (H2)-receptor antagonist-induced elevation of gastric pH on oral bioavailability of a single dose of dapsone 100 mg.
Prospective, randomized, crossover, open-label, single-dose pharmacokinetic study.
Teaching hospital.
Sixteen men were enrolled in the study; data from 11 subjects were evaluable.
Participants received two treatments separated by at least 14 days. Treatment A consisted of a single dose of dapsone 100 mg. Treatment B consisted of a single dose of dapsone 100 mg plus two doses of oral nizatidine 300 mg administered 3-4 hours apart to maintain gastric pH above 6.0. Plasma samples collected before and up to 120 hours after dapsone administration were analyzed for dapsone and monoacetyldapsone (MADDS) by high-performance liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis.
Gastric pH in the first 6 hours after dapsone administration was above 6.0 for a mean +/- SD of 1.1% +/- 2.9% of the time in the absence of nizatidine and 69.5% +/- 18.0% of the time during nizatidine therapy. The geometric mean dapsone maximum plasma concentration (Cmax) declined by 13% (p<0.01), and median time to Cmax occurred 2 hours later (p<0.01) with nizatidine coadministration compared with dapsone alone. Inclusion of the 90% confidence interval for the mean Cmax ratio within the equivalence interval of 0.8-1.25 demonstrated the lack of clinical significance for this modest decrease in Cmax. Neither the area under the dapsone plasma concentration-time curve from zero to infinity nor the elimination half-life of dapsone were significantly altered by nizatidine. No clinically significant changes were observed in the pharmacokinetics of MADDS with regard to coadministration of nizatidine.
Elevation of gastric pH by H2-receptor antagonists, such as nizatidine, does not result in clinically important changes in the rate or extent of oral dapsone absorption.
探讨组胺2（H2）受体拮抗剂引起的胃内pH值升高对单剂量100mg氨苯砜口服生物利用度的影响。
前瞻性、随机、交叉、开放标签、单剂量药代动力学研究。
教学医院。
16名男性参与本研究；11名受试者的数据可用于评估。
参与者接受两种治疗，间隔至少14天。治疗A为单剂量100mg氨苯砜。治疗B为单剂量100mg氨苯砜加两剂口服尼扎替丁300mg，间隔3 - 4小时给药，以维持胃内pH值高于6.0。在氨苯砜给药前及给药后长达120小时采集的血浆样本，通过高效液相色谱法分析氨苯砜和单乙酰氨苯砜（MADDS）。药代动力学参数通过非房室分析确定。
在无尼扎替丁时，氨苯砜给药后最初6小时内胃内pH值高于6.0的时间平均占总时间的1.1%±2.9%，而在尼扎替丁治疗期间这一比例为69.5%±18.0%。与单独使用氨苯砜相比，联合使用尼扎替丁时，氨苯砜的几何平均最大血浆浓度（Cmax）下降了13%（p<0.01），达到Cmax的中位时间延迟了2小时（p<0.01）。将平均Cmax比值的90%置信区间纳入0.8 - 1.25的等效区间内，表明Cmax的适度下降缺乏临床意义。尼扎替丁对氨苯砜血浆浓度 - 时间曲线从零到无穷大的面积以及氨苯砜的消除半衰期均无显著影响。关于联合使用尼扎替丁，MADDS的药代动力学未观察到具有临床意义的变化。
H2受体拮抗剂如尼扎替丁引起的胃内pH值升高，不会导致氨苯砜口服吸收速率或程度出现具有临床重要意义的变化。
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