Jessa M J, Goddard A F, Barrett D A, Shaw P N, Spiller R C
Department of Pharmaceutical Sciences, University of Nottingham, UK.
Br J Clin Pharmacol. 1997 Sep;44(3):245-53. doi: 10.1046/j.1365-2125.1997.t01-1-00572.x.
To evaluate the effect of omeprazole on the pharmacokinetics of metronidazole and hydroxymetronidazole in plasma, gastric juice and saliva following intravenous infusion or oral dosing of metronidazole.
Eight volunteers received single doses of metronidazole (400 mg) intravenously and orally, whilst taking placebo or omeprazole (40 mg, twice daily for 5 days) in a randomized 4-way crossover study. Metronidazole and hydroxymetronidazole concentrations in plasma, saliva and gastric juice samples were determined by h.p.l.c. Pharmacokinetic parameters for metronidazole and hydroxymetronidazole were calculated, and the significance of the mean differences in parameters between omeprazole and placebo co-administration was assessed using a two-tailed, paired t-test.
There were no significant differences (P < 0.05) in any of the plasma or saliva pharmacokinetic parameter values for metronidazole between volunteers receiving omeprazole or placebo when metronidazole was administered either as an intravenous infusion or orally. Following intravenous administration of metronidazole to the placebo group and omeprazole treated group respectively, the gastric transfer of metronidazole was significantly reduced from 15.5 +/- 10.4% to 2.6 +/- 1.0% of the dose (P = 0.007; 95% CI of difference 4.8 to 21.0) with concomitant changes in the metronidazole AUC (from 77.5 +/- 18.0 mumol l-1 h to 352.6 +/- 182.1 mumol l-1 h; P = 0.0003; 95% CI of difference 127.6 to 422.7), Cmax (from 61.4 +/- 26.5 mumol l-1 to 271.8 +/- 104.3 mumol l-1; p = 0.0001; 95% CI of difference 118.6 to 302.1). Similarly, the gastric juice AUC of hydroxymetronidazole was significantly reduced from 3.2 +/- 1.9 mumol l-1 h to 1.5 +/- 0.8 mumol l-1 h of the dose (P = 0.0043; 95% CI of difference 0.4 to 3.0) with a concomitant change in Cmax (from 5.0 +/- 2.5 mumol l-1 to 3.0 +/- 1.2 mumol l-1; P = 0.0007; 95% CI of difference 0.7 to 3.4).
Omeprazole had little effect on the plasma and salivary pharmacokinetics of metronidazole (or its hydroxymetabolite) after intravenous or oral administration, but it did have a substantial effect on the pharmacokinetics of metronidazole and hydroxymetronidazole in gastric juice.
评估奥美拉唑对甲硝唑静脉输注或口服给药后，血浆、胃液和唾液中甲硝唑及羟基甲硝唑药代动力学的影响。
在一项随机四交叉研究中，8名志愿者分别静脉注射和口服单剂量甲硝唑（400mg），同时服用安慰剂或奥美拉唑（40mg，每日两次，共5天）。采用高效液相色谱法测定血浆、唾液和胃液样本中甲硝唑和羟基甲硝唑的浓度。计算甲硝唑和羟基甲硝唑的药代动力学参数，并采用双侧配对t检验评估奥美拉唑与安慰剂联合给药时参数平均差异的显著性。
当甲硝唑静脉输注或口服给药时，接受奥美拉唑或安慰剂的志愿者之间，甲硝唑的任何血浆或唾液药代动力学参数值均无显著差异（P<0.05）。分别向安慰剂组和奥美拉唑治疗组静脉注射甲硝唑后，甲硝唑的胃内转运显著降低，从剂量的15.5±10.4%降至2.6±1.0%（P = 0.007；差异的95%置信区间为4.8至21.0），同时甲硝唑的AUC发生变化（从77.5±18.0μmol·l-1·h增至352.6±182.1μmol·l-1·h；P = 0.0003；差异的95%置信区间为127.6至422.7），Cmax（从61.4±26.5μmol·l-1增至271.8±104.3μmol·l-1；p = 0.0001；差异的95%置信区间为118.6至302.1）。同样，羟基甲硝唑的胃液AUC从剂量的3.2±1.9μmol·l-1·h显著降至1.5±0.8μmol·l-1·h（P = 0.0043；差异的95%置信区间为0.4至3.0），同时Cmax发生变化（从5.0±2.5μmol·l-1降至3.0±1.2μmol·l-1；P = 0.0007；差异的95%置信区间为0.7至3.4）。
奥美拉唑对静脉或口服给药后甲硝唑（或其羟基代谢物）的血浆和唾液药代动力学影响较小，但对胃液中甲硝唑和羟基甲硝唑的药代动力学有显著影响。
