J Clin Pharmacol
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PHARMACOKINETICS AND PHARMACODYNAMICS

Gastric Function in the Elderly: Effects on Absorption of Ketoconazole

Aryeh Hurwitz, MD, Constance E. Ruhl, MD, MPH, Bruce F. Kimler, PhD, Elizabeth M. Topp, PhD and Matthew S. Mayo, PhD

From the University of Kansas Medical Center, Department of Medicine (Dr. Hurwitz), Center on Aging (Dr. Ruhl), Department of Radiation Oncology (Dr. Kimler), Kansas Cancer Institute (Dr. Mayo), and Department of Preventive Medicine (Dr. Mayo), Kansas City, Kansas, and the University of Kansas, Department of Pharmaceutical Chemistry, Lawrence, Kansas (Dr. Topp).

The authors studied effects of age-related changes in gastric function on absorption of ketoconazole. Eighteen men and women age 65 years or older swallowed 200 mg ketoconazole on two occasions, once as tablets with water and once as tablets crushed in acidic juice. The sequence was randomly determined. Gastric pH was measured by radiotelemetry and gastric emptying rate by radiolabeled technetium with a gamma camera. Plasma ketoconazole was assayed by high-performance liquid chromatography (HPLC). Subjects with gastric pH less than or equal to 4.5 absorbed ketoconazole equally well from intact tablets and tablets crushed in acid. When pH was 5.0 or higher, ketoconazole was absorbed well from acid-crushed tablets but not from intact tablets. Gastric emptying was shown to be rapid in all subjects. Since the prevalence of such hypoacidity is approximately 5% in the elderly, and other parameters of gastric function are usually normal, impaired absorption of drugs such as ketoconazole should be uncommon with normal aging.

Key Words: Ketoconazole • gastric function • drug absorption • pharmacokinetics • elderly patients

Address for reprints: Aryeh Hurwitz, MD, Department of Internal Medicine, Division of Clinical Pharmacology, Room 4016 Wescoe, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160-7320.






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