Gastropathy and Ketoconazole Malabsorption in the Acquired Immunodeficiency Syndrome (AIDS)

Abstract

STUDY OBJECTIVE: To correlate oral ketoconazole absorption with gastric acid secretion in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective measurement of maximal acid output and oral ketoconazole absorption with and without 0.1-N hydrochloric acid. SETTING: Hospital in-patients in university medical center. PATIENTS: Ten consecutive male patients with AIDS. INTERVENTION: Maximal acid output was determined after pentagastrin stimulation in all patients. Serum ketoconazole levels were measured the day after ingestion of a 200-mg ketoconazole tablet in the fasted state. On the final day, ketoconazole was ingested with 200 mL of 0.1-N hydrochloric acid. MEASUREMENTS AND MAIN RESULTS: Maximal acid output was below 15 mEq/h in 7 of 10 patients. In all 7, the area under the serum ketoconazole concentration-time curve was below normal (1.4 +/- 0.9 mg/h.L; mean +/- SE), and absorption was normalized by hydrochloric acid (9.9 +/- mg/h.L). Two of three patients with maximal acid outputs above 15 mEq/h had normal ketoconazole absorption (15.1 +/- 6.7 mg/h.L). CONCLUSIONS: The bioavailability of oral ketoconazole is reduced in patients with AIDS, largely as a result of gastric hypochlorhydria. Ketoconazole tablets should therefore be given with acid in these patients.