The Effect of Verapamil on the Nephrotoxic Potential of Gentamicin as Measured by Urinary Enzyme Excretion in Healthy Volunteers

The effects of verapamil on the nephrotoxic potential of multiple‐dose gentamicin were studied in healthy adult male volunteers. Subjects received a gentamicin infusion every 8 hours for 19 doses. Gentamicin dosage was adjusted to maintain peak concentrations of 5.5 mg/L and trough concentrations of 0.5 mg/L. Verapamil was given as a sustained release preparation of 180 mg twice daily starting 2 days before the aminoglycoside, and continued for 4 days post‐gentamicin therapy. Nephrotoxicity was assessed by measuring 24‐hour urinary alanine aminopeptidase excretion (AAP). The urinary AAP results of six subjects given gentamicin with verapamil were compared with urinary AAP from nine subjects treated with gentamicin alone. These nine subjects were matched with the verapamil‐treated subjects on the basis of gentamicin area‐under‐the‐curve (AUC). After matching AUC, gentamicin exposure was virtually identical between the two groups with an average gentamicin AUC of 26.61 ± 1.49 and 27.51 ± 1.25 mg · hr/L for the gentamicin/ve‐rapamil and gentamicin only groups respectively. Verapamil retarded the rise in mean daily AAP excretion on days 1 to 6 of gentamicin therapy, with a significant difference with respect to AAP urinary excretion (P < .05) observed on day 2. There was no significant difference in total cumulative AAP excretion or in the time to return to baseline AAP excretion. Therefore, verapamil was effective in reducing AAP excretion associated with gentamicin therapy. 1995 American College of Clinical Pharmacology