The clearance of antipyrine and indocyanine green in normal subjects and in patients with chronic liver disease

The pharmacokinetics after oral administration of 1,200 mg antipyrine and intravenous administration of 0.5 mg/kg indocyanine green have been investigated in 6 normal subjects and in 20 patients with chronic liver disease of varying etiology. Severe impairment of liver junction associated with a decrease in serum albumin, elevation in serum bilirubin, or prolongation in prothrombin time correlated with a fall in the clearance of both drugs. The clearances of the two drugs correlated well in normal subjects and in patients with chronic liver disease. The presence of a surgical portacaval anastomosis was associated with a lower indocyanine green clearance for comparable clearance of antipyrine. The concept of functioning hepatic parenchymal mass is proposed as a common rate‐limiting parameter for the elimination of the two drugs.

[1]  J. J. Curry,et al.  THE ESTIMATION OF HEPATIC BLOOD FLOW IN MAN. , 1945, The Journal of clinical investigation.

[2]  R. Swartz,et al.  Effects of physical stress on the disposition of drugs eliminated by the liver in man. , 1974, The Journal of pharmacology and experimental therapeutics.

[3]  R. Branch,et al.  Hemodynamic drug interactions: the reduction of oxyphenbutazone clearance by dl-propranol in the dog. , 1973, The Journal of pharmacology and experimental therapeutics.

[4]  E. Vesell,et al.  Comparison of plasma levels of antipyrine, tolbutamide, and warfarin after oral and intravenous administration , 1974, Clinical pharmacology and therapeutics.

[5]  W. I. Cranston,et al.  Hepatic Uptake and Biliary Excretion of Indocyanine Green in the Dog.∗ , 1958, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[6]  P. Astrup,et al.  Plasma antipyrine half-life and hepatic microsomal antipyrine hydroxylase activity in rabbits. , 1973, Pharmacology.

[7]  J. Crooks,et al.  Effect of Age and Sex on Human Drug Metabolism , 1971, British medical journal.

[8]  B. Brodie,et al.  The fate of antipyrine in man. , 1950, The Journal of pharmacology and experimental therapeutics.

[9]  M. Rowland,et al.  Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. , 1968, Journal of pharmaceutical sciences.

[10]  M. Garimoldi,et al.  Kinetics of rifampicin and isoniazid administered alone and in combination to normal subjects and patients with liver disease , 1972, Gut.

[11]  N. Tygstrup,et al.  Galactose blood clearance as a measure of hepatic blood flow. , 1958, Clinical science.

[12]  S. Sherlock,et al.  Phenylbutazone and isoniazid metabolism in patients with liver disease in relation to previous drug therapy. , 1968, Lancet.

[13]  G. Mawer,et al.  Metabolism of amylobarbitone in patients with chronic liver disease , 1972, British journal of pharmacology.

[14]  L. Ranek,et al.  Clearance of Antipyrine‐Dependence of Quantitative Liver Function , 1974, European journal of clinical investigation.

[15]  R. Branch,et al.  A study of factors influencing drug disposition in chronic liver disease, using the model drug (+)-propranolol. , 1976, British journal of clinical pharmacology.

[16]  R. Branch,et al.  The reduction of lidocaine clearance by dl-propranolol: an example of hemodynamic drug interaction. , 1973, The Journal of pharmacology and experimental therapeutics.

[17]  S. Shaldon,et al.  The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. , 1961, Clinical science.

[18]  B. Brodie,et al.  The estimation of antipyrine in biological materials. , 1949, The Journal of biological chemistry.

[19]  T. Reynolds,et al.  Hepatic wedge pressure, blood flow, vascular resistance and oxygen consumption in cirrhosis before and after end-to-side portacaval shunt. , 1958, The Journal of clinical investigation.

[20]  P. Turner,et al.  Effect of phenobarbitone on hepatic drug-metabolizing enzymes and urinary D-glucaric acid excretion in man. , 1975, British journal of clinical pharmacology.

[21]  C. S. Davidson,et al.  Indocyanine green: observations on its physical properties, plasma decay, and hepatic extraction. , 1960, The Journal of clinical investigation.

[22]  H. Elias,et al.  Vascular pattern of the cirrhotic liver. , 1952, American journal of clinical pathology.

[23]  Grant R. Wilkinson,et al.  A physiological approach to hepatic drug clearance , 1975 .

[24]  T. Whitsett,et al.  The effect of hepatic blood flow on the hepatic removal rate of oxyphenbutazone in the dog. , 1971, The Journal of pharmacology and experimental therapeutics.

[25]  C. M. Leevy,et al.  Estimation of hepatic blood flow with indocyanine green. , 1962, The Journal of clinical investigation.