EFFECTS OF SPONTANEOUS GASTRIC HYPOACIDITY ON THE PHARMACOKINETICS OFZIDOVUDINE AND DIDANOSINE

Study Objective. To determine the effect of spontaneous gastric hypoac idity on the pharmacokinetics of zidovudine and didanosine in subjects infected with the human immunodeficiency virus (HIV). Design. Control led, open-label, single-dose, pharmacokinetic study. Subjects. Thirty- two asymptomatic HIV-infected subjects. Interventions. Gastric pH stud ies were conducted in all 32 subjects, and 20 of these subjects (8 wom en, 12 men) were enrolled into the pharmacokinetic study. They were st ratified into two groups according to fasting gastric pH: those withou t and with gastric hypoacidity (minimum gastric pH < 3 and greater tha n or equal to 3, respectively). Gastric pH was measured using the Heid elberg pH monitoring system in all subjects before and during pharmaco kinetic analysis of zidovudine 100 mg or didanosine 200 mg (given as t wo 100-mg tablets dissolved in 6 oz water). Plasma samples were collec ted 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 t wo occasions, and the remaining 2 had variable gastric pH. Although ga stric pn was unchanged during the administration of zidovudine, it inc reased to greater than 9 in 11 of 12 subjects with didanosine, regardl ess of baseline value. For both drugs, there were no statistically sig nificant differences in peak plasma concentration (C-max), time to rea ch 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-infinity)) between subjects with and without gastric hypoacidity despite sufficient statistical power to detect a 56% diffe rence in clearance for either drug (alpha 0.05, beta 0.1). Conclusion. Gastric hypoacidity occurs in approximately 20% of HIV-infected patie nts and does not appear to influence zidovudine or didanosine pharmaco kinetics.