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.