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.