Pharmacokinetics of minoxidil in patients with cirrhosis and healthy volunteers.
OBJECTIVE
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.


CONCLUSIONS
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.
Adams
M H
MH
Department of Pharmacy and Pharmaceutics, Virginia Commonwealth University/Medical College of Virginia, Richmond, USA. madams@kospharm.com
Poynor
W J
WJ
Garnett
W R
WR
Karnes
H T
HT
Ferry
J J
JJ
Ryan
K K
KK
Sarkar
M A
MA
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D000983:Antipyrine / Q000493:pharmacokinetics; D019540:Area Under Curve; D001711:Biotransformation; D004396:Coloring Agents / Q000493:pharmacokinetics; D005260:Female; D018757:GABA Modulators / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007208:Indocyanine Green / Q000493:pharmacokinetics; D008103:Liver Cirrhosis / Q000378:metabolism*; D008111:Liver Function Tests; D008140:Lorazepam / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D008914:Minoxidil / Q000493:pharmacokinetics*; D014665:Vasodilator Agents / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004396:Coloring Agents; D018757:GABA Modulators; D014665:Vasodilator Agents; D008914:Minoxidil; D007208:Indocyanine Green; D008140:Lorazepam; D000983:Antipyrine