Delavirdine Malabsorption in HIV‐Infected Subjects with Spontaneous Gastric Hypoacidity

Abstract

To determine the impact of gastric hypoacidity and acidic beverages on delavirdine mesylate pharmacokinetics in HIV-infected subjects, matched subjects with (n = 11) and without (n = 10) gastric hypoacidity received delavirdine 400 mg tid with either water or an acidic beverage (usually orange juice). The pharmacokinetics of delavirdine and its N-desalkyl metabolite were determined over 8 hours after 14 days of each treatment. Gastric pH was measured at baseline and during each pharmacokinetic evaluation. Delavirdine exposure (Cmax, AUC0-->8 h, and Cmin) was approximately 50% lower and the extent of delavirdine metabolism was higher in subjects with gastric hypoacidity. Orange juice produced a lower mean gastric pH compared to water and increased delavirdine absorption by 50% to 70% in subjects with gastric hypoacidity. However, orange juice had a marginal impact on delavirdine exposure in subjects without gastric hypoacidity. HIV-infected subjects with gastric hypoacidity significantly malabsorb delavirdine. Delavirdine administration with acidic beverages improves, but dose not normalize, absorption in these subjects.

Systematic review: Heliocobacter pylori infection and impaired drug absorption

“…The sample size for most of the studies was small with four studies examining fewer than 50 patients. 18,19,21,22 Only one of the retrieved studies was placebo-controlled. 18 In one study, pharmacokinetic data are not available and drug absorbtion was deduced by the daily requirement of thyroxine and ⁄ or the thyrotropin levels.…”

“…20 In all selected studies, the presence of H. pylori infection was concomitant to the presence of other diseases: Parkinson's disease, 18, 19 multinodular goitre 20 and HIV infection. 21,22 In three studies, the presence of H. pylori infection was assessed by serology only 18,21,22 and in two studies, the assessment of H. pylori status was completed by histological examination of gastric biopsies. 19,20 Gastric acid secretion was assessed in only three studies, [20][21][22] which included the measurement of fasting gastrin and ⁄ or gastric secretion studies after pentagastrin stimulation 20 or the measurement of gastric pH by a consumable radiotelemetric device.…”

“…19,20 Gastric acid secretion was assessed in only three studies, [20][21][22] which included the measurement of fasting gastrin and ⁄ or gastric secretion studies after pentagastrin stimulation 20 or the measurement of gastric pH by a consumable radiotelemetric device. 21,22 As regards the type of intervention, in three studies, 18,19,21 the absorption of the drug was investigated before and after eradication treatment in all patients, in one study 20 the effect of eradication therapy on drug absorption was evaluated only in a subset of patients 22 and in two studies, 20,22 the absorption of the drug was investigated with respect to gastric acidity. Thus, in the selected studies, the study design addressed only in part the mechanisms of oral drug absorption.…”

“…We identified two studies conducted by the same group of authors 21,22 who evaluated the role of hypochlorhydria in the absorption of delavirdine in H. pylori-positive subjects with concomitant HIV-seropositivity. Delavirdine is a non-nucleoside reverse transcriptase inhibitor with potent in vitro activity against HIV-1 and is currently approved by the Food and Drug Administration as a component of combination therapy with appropriate antiretroviral agents for the treatment of HIV-1 infection.…”

“…Searching the reference lists of potential relevant articles and pertinent reviews, we identified another study for which we obtained the full text. Thus, a total of five studies were selected for review of the full paper: [18][19][20][21][22] one was a randomized controlled trial, 19 two were controlled crossover studies, 18,22 one was a case-control study 20 and one was a case series. 21 Four studies met the criteria for having a high weight rating and one for a moderate weight rating of clinical evidence.…”