PHARMACOKINETICS OF MINOXIDIL IN PATIENTS WITH CIRRHOSIS AND HEALTHY-VOLUNTEERS

Objectives: To determine the effect of reduced hepatic function on the pharmacokinetics of minoxidil. The pharmacokinetics of antipyrine, lo razepam, and indocyanine green were included as indicators of hepatic function. Methods: Eight mild cirrhotics and eight healthy subjects re ceived antipyrine (po), lorazepam (IV), indocyanine green (IV) and min oxidil 5 mg (po). Blood and urine were sampled for up to 72 h after ea ch drug, and drug concentrations were measured by validated HPLC metho ds. Blood pressure and heart rate were measured for safety. Results: F or unchanged minoxidil, the serum elimination rate constant was signif icantly smaller and mean residence time was significantly longer in ci rrhotic patients. Urinary elimination rate constant for minoxidil gluc uronide was significantly smaller and fraction of dose excreted in uri ne was significantly higher in cirrhotic patients. Antipyrine eliminat ion was significantly slower for cirrhotic patients, No differences we re observed in lorazepam pharmacokinetic parameters. Conclusion: Pharm acokinetic analysis suggests a longer dosage interval may be appropria te in patients with hepatic impairment. In the absence of multiple-dos e minoxidil pharmacodynamic studies in this population, minoxidil shou ld be used as in other populations: begin with a modest dose, and adju st the dose based on clinical response. (C) 1998 John Wiley & Sons, Lt d.