The influence of chronic lobular hepatitis on pharmacokinetics of cefoperazone—a novel galactose single‐point method as a measure of residual liver function

Oliver Yoa‐Pu Hu, Hung‐Shang ‐S Tang, Ching‐Ling ‐L Chang

研究成果: 雜誌貢獻文章同行評審

9 引文 斯高帕斯(Scopus)

摘要

Cefoperazone is a semisynthetic cephalosporin antibiotic containing a piperazine side chain, which results in antipseudomonal activity. Unlike the other cephalosporins, it is mainly cleared by the liver (60–80%) and it may be more sensitive to changes in the liver function and/or plasma protein binding than other cephalosporins, which are not primarily cleared by the liver. In order to study the influence of chronic lobular hepatitis on the pharmacokinetics of cefoperazone, a dose of 1 g of cefoperazone was administered to 11 normal, healthy volunteers and 16 subjects with chronic lobular hepatitis. In each volunteer or patient, a novel galactose single‐point (GSP) method, the galactose elimination capacity (GEC) test, and the modified galactose elimination capacity (MGEC) test were also performed as a measure of residual liver function. Cefoperazone was administered intravenously over a period of 3–5 min. Blood and urine samples were collected at appropriate intervals after drug administration and stored at −30°C until high‐pressure liquid chromatographic (HPLC) analysis. The cefoperazone hepatic clearance, mean residence time, and renal clearance in hepatitis patients were significantly different from those of normal healthy volunteers, whereas the plasma protein binding was unaltered between the two groups. Urinary excretion of cefoperazone showed a highly significant increase in patients, 23.95 ± 5.06% and 37.54 ± 13.61% for normal men and hepatitis patients respectively. Hepatic clearance and fraction excreted in urine significantly correlated with values of GSP and MGEC respectively (p <0.05). These results suggest (i) cefoperazone kinetics was significantly altered in patients with chronic lobular hepatitis; (ii) GSP, a novel simple, clinically useful quantitative liver function test, can predict the cefoperazone hepatic clearance in patients with liver dysfunction.
原文英語
頁(從 - 到)563-576
頁數14
期刊Biopharmaceutics & Drug Disposition
15
發行號7
DOIs
出版狀態已發佈 - 一月 1 1994
對外發佈Yes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

指紋 深入研究「The influence of chronic lobular hepatitis on pharmacokinetics of cefoperazone—a novel galactose single‐point method as a measure of residual liver function」主題。共同形成了獨特的指紋。

引用此