The influence of chronic lobular hepatitis on pharmacokinetics of cefoperazone--a novel galactose single-point method as a measure of residual liver function.
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 degrees 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.
School of Pharmacy, National Defence Medical Centre, Taipei, Republic of China.
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Tang
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Chang
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D002438:Cefoperazone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D005690:Galactose / Q000378:metabolism*; D006521:Hepatitis, Chronic / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011485:Protein Binding
D015415:Biomarkers; D001798:Blood Proteins; D002438:Cefoperazone; D005690:Galactose