Steady-state pharmacokinetics of nitrendipine in hepatic insufficiency.
As a calcium antagonist, nitrendipine will be used in the treatment of various diseases in patients with hepatic insufficiency, and it is important to know if they require modified dosing schedules. In this study, six patients with biopsy-confirmed cirrhosis and six age/sex-matched normal healthy subjects were given 10 mg nitrendipine as a single dose on day 1 and 10 mg nitrendipine every 12 h from day 3 through the first dose on day 8. Blood levels of nitrendipine were determined to confirm the attainment of steady state and evaluate the pharmacokinetics in each group. Nitrendipine concentrations were consistently higher in the hepatic group. On day 1, the maximum concentration (Cmax) in the normals was 4.67 +/- 2.60 ng/ml and in the hepatic patients 16.87 +/- 9.42 ng/ml. On day 8, these values were 8.60 +/- 8.82 ng/ml and 27.37 +/- 8.56 ng/ml, respectively. The time to Cmax was not significantly different in the two groups. The elimination half-life was only slightly prolonged from 15.29 +/- 7.25 h in the normals to 19.57 +/- 4.28 h in the hepatic impairment group. This resulted in a marked increase in the area under the concentration-time curve from 28.71 +/- 28.92 ng . h/ml for the normals to 119.56 +/- 34.39 ng . h/ml for the hepatic patients on day 1 and similar results on day 8. Trough levels at steady state were expectedly higher in the hepatic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D006801:Humans; D007700:Kinetics; D008107:Liver Diseases / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D009568:Nitrendipine; D011674:Pulse / Q000187:drug effects
D002121:Calcium Channel Blockers; D009568:Nitrendipine; D009543:Nifedipine