The effect of cirrhosis on the disposition and elimination of clindamycin.
This study assessed the effect of alcoholic cirrhosis in man and of experimental liver injury in rats on the disposition and elimination of clindamycin. In 7 cirrhotics a statistically significant, although modest, prolongation of clindamycin half-life (T1/2beta) was observed as compared to values in 7 age-matched normal contrals (mean plus or minus SD: 4.46 plus or minus 0.93 hr vs 3.42 plus or minus 0.45 hr, P equals 0.02). This was primarily due to a decrease in clindamycin serum clearance in the cirrhotics, since the volume of distribution of the drug was similar in both groups (P more than 0.05). Serum protein binding of clindamycin was of the order of 79% and was comparable in both groups (P more than 0.05). There was a significant correlation between the T1/2beta of the drug and both total serum bilirubin and SGOT. The T1/2beta of clindamycin was also prolonged in rats with acute hepatic necrosis induced by administration of carbon tetrachloride and those with acute cholestasis caused by common bile duct ligation. These data suggest that liver damage, both chronic and acute, impairs the elimination of clindamycin but that this effect is small.
D000328:Adult; D000437:Alcoholism / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism; D002779:Cholestasis / Q000378:metabolism; D002981:Clindamycin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011517:Prothrombin Time; D051381:Rats; D012709:Serum Albumin / Q000032:analysis
D012709:Serum Albumin; D002981:Clindamycin; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D001663:Bilirubin