Study Objective. To determine the effect of spontaneous gastric hypoacidity on the pharmacokinetics of zidovudine and didanosine in subjects infected with the human immunodeficiency virus (HIV). Design. Controlled, open-label, single-dose, pharmacokinetic study. Subjects. Thirty-two asymptomatic HIV-infected subjects. Interventions. Gastric pH studies were conducted in all 32 subjects, and 20 of these subjects (8 women, 12 men) were enrolled into the pharmacokinetic study. They were stratified into two groups according to fasting gastric pH: those without and with gastric hypoacidity (minimum gastric pH < 3 and ≤ 3, respectively). Gastric pH was measured using the Heidelberg pH monitoring system in all subjects before and during pharmacokinetic analysis of zidovudine 100 mg or didanosine 200 mg (given as two 100-mg tablets dissolved in 6 oz water). Plasma samples were collected over 8 hours after dosing. Measurements and Main Results. Six (20%) of 30 subjects had a minimum gastric pH of 3 or above on at least two occasions, and the remaining 2 had variable gastric pH. Although gastric pH was unchanged during the administration of zidovudine, it increased to greater than 9 in 11 of 12 subjects with didanosine, regardless of baseline value. For both drugs, there were no statistically significant differences in peak plasma concentration (C(max)), time to reach peak plasma concentration (T(max)), elimination rate constant (k(e)), and area under the plasma concentration-time curve from time zero to infinity (AUC(0-∞)) between subjects with and without gastric hypoacidity despite sufficient statistical power to detect a 56% difference in clearance for either drug (α 0.05, β 0.1). Conclusion. Gastric hypoacidity occurs in approximately 20% of HIV- infected patients and does not appear to influence zidovudine or didanosine pharmacokinetics.
|Number of pages||7|
|State||Published - May 1997|