Pharmacokinetics of Rifapentine in Patients with Varying Degrees of Hepatic Dysfunction

• Published in: Journal of clinical pharmacology Vol. 38; no. 6; pp. 517 - 524
• Main Authors: Keung, Anther C. F., Eller, Mark G., Weir, Scott J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-06-1998; Sage Science
• Subjects: Adolescent; Adult; Aged; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - administration & dosage; Antitubercular Agents - blood; Antitubercular Agents - pharmacokinetics; Area Under Curve; Biological and medical sciences; Female; Humans; Liver Diseases - metabolism; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Rifampin - administration & dosage; Rifampin - analogs & derivatives; Rifampin - blood; Rifampin - pharmacokinetics; Human; Liver failure; Metabolite; Dysfunction; Single dose; Oral administration; Digestive diseases; Hepatic disease; Antituberculous agent; Pharmacokinetics; Rifapentine
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1002/j.1552-4604.1998.tb05789.x

In this open‐label investigation, the pharmacokinetics of rifapentine and its active metabolite, 25‐desacetyl‐rifapentine, were characterized in patients with varying degrees of hepatic dysfunction. Eight patients with mild‐to‐moderate chronic, stable hepatic dysfunction and seven patients with moderate‐to‐severe hepatic dysfunction received single oral 600‐mg doses of rifapentine. Maximum plasma concentration of rifapentine was lower, time to maximum plasma concentration (tmax) was greater, and elimination half‐life (t1/2) was longer in the patients with moderate‐to‐severe hepatic dysfunction than in those with mild‐to‐moderate dysfunction. However, mean area under the concentration—time curve extrapolated to infinity (AUC0–∞) for the two groups was similar. AUC0–∞ values in patients with hepatic dysfunction were 19% to 25% higher than values previously reported for healthy volunteers. The 25‐desacetyl metabolite appeared in plasma slowly after the single oral dose of rifapentine. Similar to findings for the parent drug, comparable plasma exposures of 25‐desacetyl‐rifapentine based on AUC0–∞ were found in the two groups of patients with mild‐to‐moderate and moderate‐to‐severe hepatic dysfunction. Rifapentine was well tolerated in this patient population, irrespective of the etiology or severity of hepatic dysfunction. These safety and pharmacokinetic results suggest that no dosage adjustments for rifapentine are needed in patients with hepatic impairment.