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Pharmacokinetics of minoxidil in patients with cirrhosis and healthy volunteers
Author(s) -
Adams Marijke H.,
Poynor Wesley J.,
Garnett William R.,
Karnes H. T.,
Ferry James J.,
Ryan Kristi K.,
Sarkar Mohamadi A.
Publication year - 1998
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(1998110)19:8<501::aid-bdd127>3.0.co;2-g
Subject(s) - pharmacokinetics , minoxidil , elimination rate constant , medicine , indocyanine green , pharmacology , cirrhosis , population , liver function , urine , volume of distribution , surgery , environmental health
Objectives : To determine the effect of reduced hepatic function on the pharmacokinetics of minoxidil. The pharmacokinetics of antipyrine, lorazepam, and indocyanine green were included as indicators of hepatic function. Methods : Eight mild cirrhotics and eight healthy subjects received antipyrine (po), lorazepam (IV), indocyanine green (IV) and minoxidil 5 mg (po). Blood and urine were sampled for up to 72 h after each drug, and drug concentrations were measured by validated HPLC methods. Blood pressure and heart rate were measured for safety. Results : For unchanged minoxidil, the serum elimination rate constant was significantly smaller and mean residence time was significantly longer in cirrhotic patients. Urinary elimination rate constant for minoxidil glucuronide was significantly smaller and fraction of dose excreted in urine was significantly higher in cirrhotic patients. Antipyrine elimination was significantly slower for cirrhotic patients. No differences were observed in lorazepam pharmacokinetic parameters. Conclusion : Pharmacokinetic analysis suggests a longer dosage interval may be appropriate in patients with hepatic impairment. In the absence of multiple‐dose minoxidil pharmacodynamic studies in this population, minoxidil should be used as in other populations: begin with a modest dose, and adjust the dose based on clinical response. Copyright © 1998 John Wiley & Sons, Ltd.