Adams M H, Poynor W J, Garnett W R, Karnes H T, Ferry J J, Ryan K K, Sarkar M A
Department of Pharmacy and Pharmaceutics, Virginia Commonwealth University/Medical College of Virginia, Richmond, USA.
Biopharm Drug Dispos. 1998 Nov;19(8):501-15. doi: 10.1002/(sici)1099-081x(1998110)19:8<501::aid-bdd127>3.0.co;2-g.
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.
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.
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.
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.
确定肝功能降低对米诺地尔药代动力学的影响。将安替比林、劳拉西泮和吲哚菁绿的药代动力学作为肝功能指标。
8名轻度肝硬化患者和8名健康受试者接受安替比林（口服）、劳拉西泮（静脉注射）、吲哚菁绿（静脉注射）和5毫克米诺地尔（口服）。每种药物给药后最多72小时采集血样和尿样，采用经过验证的高效液相色谱法测量药物浓度。测量血压和心率以确保安全。
对于未代谢的米诺地尔，肝硬化患者的血清消除速率常数显著较小，平均驻留时间显著较长。肝硬化患者中米诺地尔葡萄糖醛酸苷的尿排泄速率常数显著较小，尿中排泄的剂量分数显著较高。肝硬化患者的安替比林消除明显较慢。劳拉西泮药代动力学参数未观察到差异。
药代动力学分析表明，肝功能损害患者可能适合延长给药间隔。鉴于该人群中尚未进行米诺地尔多剂量药效学研究，米诺地尔应像在其他人群中一样使用：从适度剂量开始，并根据临床反应调整剂量。
