PHARMACOKINETICS OF CEFOPERAZONE IN LIVER DISEASES

• Published in: Japanese journal of antibiotics 1985/08/25, Vol.38(8), pp.2026-2032
• Main Authors: KAKIUCHI, SATOSHI, TAGAWA, SHINSEI, KOSAKA, YOSHITANE, TAMEDA, YUKIHIKO
• Format: Article
• Language: Japanese
• Subjects: Adolescent; Adult; Aged; Cefoperazone - metabolism; Female; Humans; Kinetics; Liver Diseases - metabolism; Male
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.38.2026

To obtain useful informations for determining the optimal dosage of drugs in patients with impaired liver function, pharmacokinetics of cefoperazone (CPZ) was studied in healthy adults (normal control group) and 35 patients with liver disease (liver disease group). CPZ is a new third generation cephalosporin which is mainly excreted into the bile and has serum half-life of about 2 hours. After a rapid intravenous injection of CPZ, peripheral blood and urine samples were obtained at the time according to the protocol of this study. Serum and urine concentrations of CPZ were determined by the bioassay method using Micrococcus luteus ATCC 9341 as the test strain. From the concentrations of CPZ in serum and urine, pharmacokinetic parameters were calculated by means of a “ two-compartment open model ”. After an administration of CPZ, the serum concentration declined more slowly in the liver disease group as compared to the normal control group. At 1 hour after intravenous injection of CPZ, the difference of the serum level was already observed between these 2 groups. The half-life of elimination (T 1/2) was 2 to 4 times longer in the liver disease group. The elimination rate constant (K10) and total clearance (CI,) of CPZ were much lower in the liver disease group than in the control group except for hepatocellular carcinoma. On the other hand, urinary excretion rate (Ur) was lower in the normal control group than in the liver disease group. There was a close correlation between disappearance rate of indocyanine green (KICG) and parameterssuch as T1/2, K10, CIt and Cler with coefficients of-0. 642, 0. 723, 0. 690 and 0. 682, respectively. Furthermore, creatinine clearance (Ccr.) and liver function tests (albumin and gammaglobulin) were also correlated closely to those pharmacokinetic parameters. From these results, it was suggested that pharmacokinetics of CPZ was strongly affected by impaired liver function. In many liver function tests, Kiec was a valuable parameter to determine the dosage of drugs in case of liver disease, because of close correlations with pharmacokinetic parameters of CPZ. Finally, it should be remembered that in patients with liver disease associated with renal dysfunction the alteration of pharmacokinetics of CPZ may be emphasized by decreased urinary excretion.