The effect of cirrhosis on the steady-state pharmacokinetics of oral ciprofloxacin.
The pharmacokinetics of ciprofloxacin, a carboxyquinolone, was studied after oral administration of the drug to seven patients with biopsy-proved cirrhosis and to seven healthy volunteers. Serum concentrations of ciprofloxacin and its three metabolites--desethylene ciprofloxacin (M1), sulfociprofloxacin (M2), and oxociprofloxacin (M3)--were measured by an HPLC procedure. The pharmacokinetic parameters for ciprofloxacin were not significantly altered in cirrhotic patients. The elimination half-life (t 1/2) and the area under the serum concentration versus time curve (AUC) were, respectively, 3.71 hours and 16.18 microgram.ml-1.hr-1 in the normal subjects and 3.47 hours and 18.38 micrograms.ml-1.hr-1 in patients with cirrhosis. The formation of oxociprofloxacin was reduced by approximately one half in the cirrhotic subjects, as the Cmax was 0.29 micrograms/ml in normal subjects versus 0.14 micrograms/ml in cirrhotic patients and the mean AUC(0-t) was 1.54 micrograms.ml-1.hr-1 in normal subjects versus 0.70 micrograms.ml-1.hr-1 in cirrhotic patients. However, there appeared to be no significant difference between groups with respect to desethylene ciprofloxacin and sulfociprofloxacin. Therefore it appears from this study that no dosage adjustment is required in patients with hepatic cirrhosis.
Frost
R W
RW
Clinical Pharmacology Associates, Inc., Miami, Fla.
Lettieri
J T
JT
Krol
G
G
Shamblen
E C
EC
Lasseter
K C
KC
D000284:Administration, Oral; D000368:Aged; D000890:Anti-Infective Agents; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; C054029:ciprofloxacin-7-ethylenediamine; C060059:oxociprofloxacin; C060058:sulfociprofloxacin; D002939:Ciprofloxacin