Influence of hepatic insufficiency in pharmacokinetics of drugs: example for an anthranilic diuretic.
Hepatic insufficiency is responsible for numerous modifications of drug metabolism and pharmacokinetics, because the liver is the most important organ for the transformation and, with the kidney, elimination of drugs. Pharmacokinetics of furosemide, an anthranilic diuretic, was compared in normal subjects and cirrhotics with hepatic insufficiency, after oral administration. In patients, we observed few modifications of the bioavailability. The total elimination of the drug was normal when the urinary excretion compensated a slight reduction in biliary secretion, but when this reduction was important the total clearance of furosemide decreased. In urine, the elimination time was lengthened, but the percentage of excretion was about the same as for normal subjects. The pharmacological effects were also modified for cirrhotics with decrease of sodium and water excretion, for the same blood concentration of drug as in controls. Also, we observed a shift between the salidiuretic effect and the blood concentration in patients, when there was an exact concordance of these times in control subjects. Two hypotheses have been proposed to explain this phenomenon: (1) modifications in hepatic metabolism or, (2) in drug protein binding.
D000328:Adult; D000368:Aged; D005665:Furosemide / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D005665:Furosemide