Dosage adjustment of ribavirin based on renal function in Japanese patients with chronic hepatitis C.
The daily dose of ribavirin is currently determined based on body weight. In the present study, the authors examined factors influencing total plasma clearance (CL(total)) and the toxic level on red blood cells of ribavirin in such body weight-based dosage adjustment in Japanese chronic hepatitis C patients (13 male and 6 female). Patients received ribavirin (600 or 800 mg/d) orally, depending on their body weights, together with interferon alpha-2b (6 million units) intramuscularly. A steady-state trough plasma concentration (C(pss)) was achieved approximately 4 weeks after the initiation of treatment, but the value was scattered among patients in a range from 1100 to 4200 ng/mL. The high C(pss) of ribavirin of approximately 4000 ng/mL decreased hemoglobin concentrations to less than 8.5 g/dL. The individual CL(total), estimated by dividing dose normalized by body weight by C(pss), of ribavirin correlated significantly with the patient's creatinine clearance. In contrast, no relationship was observed with other parameters such as age, body weight, serum creatinine concentration, alanine aminotransferase (ALT) concentration, or aspartate aminotransferase (AST) concentration, though ALT and AST concentrations decreased with ribavirin treatment in most patients. These results indicate that CL(total) of ribavirin is dependent on renal function (creatinine clearance), and hemolysis is induced by high ribavirin concentrations in plasma. Dosage adjustment of ribavirin based on renal function and body weight would provide effective and safer treatment without causing hemolysis.
Maeda
Yorinobu
Y
Department of Pharmacy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. mae@db3.so-net.ne.jp
Kiribayashi
Yoshie
Y
Moriya
Takashi
T
Maruhashi
Akira
A
Omoda
Kei
K
Funakoshi
Sachiyo
S
Murakami
Teruo
T
Takano
Mikihisa
M
D000328:Adult; D000368:Aged; D000465:Algorithms; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000998:Antiviral Agents; D012254:Ribavirin