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.

No abstract

No abstract

No abstract

No abstract

No abstract

No abstract

Effects of co-administration of cimetidine(CMT) on pharmacokinetic behaviors of chlorpropamide(CPA),an oral hypoglycemic agent,after intravenous injection,were investigated in rabbits.The co-administration of CMT enhanced the plasma concentration of CPA,and reduced the amount of cumulative urinary excretion of CPA after intravenous bolus injection.Furthermore,the co-administration of CMT was found to decrease the renal clearance of CPA significantly,but to have no effect on its extrarenal clearance.These clearly indicate that the interaction of CPA with CMT is generated during renal excretion.For the purpose of elucidating the cause,effects of CMT on plasma protein binding of CPA,glomerular filtration rate (GFR),renal tubular secretion of PSP,and urinary pH were investigated.Plasma protein binding of CPA,GFR,and urinary pH were unchanged with and without CMT.But urinary excretion of PSP was decreased by co-administration of CMT.These observations suggest that the co-administration of CMT may depress the renal excretion of CPA by inhibiting the tubular secretion.