Single-dose pharmacokinetics of nefazodone in healthy young and elderly subjects and in subjects with renal or hepatic impairment

✍ Scribed by R. H. Barbhaiya; D. S. Greene; U. A. Shukla

• Publisher: Springer
• Year: 1995
• Tongue: English
• Weight: 658 KB
• Volume: 49
• Category: Article
• ISSN: 0031-6970
• DOI: 10.1007/bf00192383

✦ Synopsis

The single-dose pharmacokinetics of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were examined in 12 healthy younger subjects < 55 years of age (YNG), 12 elderly subjects > 65 years of age (ELD), 12 patients with biopsy proven hepatic cirrhosis (HEP) and 12 patients with moderate renal impairment (REN), ClcR 20 60 ml rain -1 . The study was of parallel group design, with each of the four subject groups receiving escalating single oral doses of 50, 100 and 200 mg of nefazodone at 1 week intervals. Serial blood samples for pharmacokinetic analysis were collected for 48 h following each dose and plasma samples were assayed for NEE HO-NEF and mCPP by a validated HPLC method.

Single oral doses up to 200 mg of nefazodone were well tolerated by all subjects. Maximum plasma levels of NEF and HO-NEF were generally attained within 1 h after administration of nefazodone. HO-NEF and mCPP plasma levels were about 1/3 and < 1/10 those of NEF, respectively. There were no apparent genderrelated pharmacokinetic differences in any group of subjects. NEF and HO-NEF pharmacokinetics were dose dependent in all four subject groups; a superproportional increase in AUC and an increase in t~ with increasing dose was obtained, indicative of nonlinear pharmacokinetics. Relative to normal subjects, elderly and cirrhotic subjects exhibited increased systemic exposure to NEF and HO-NEF, as reflected by AUC, at all doses ofnefazodone; subjects with moderate renal impairment did not.