Pharmacokinetics of enoxacin and its oxometabolite following intravenous administration to patients with different degrees of renal impairment.
Enoxacin is a fluorinated quinolone with potential clinical use in the treatment of serious infections. Twenty-three patients (age, 19 to 87 years) with different degrees of renal function, including a group undergoing chronic hemodialysis, received enoxacin (400 mg) by intravenous infusion (1 h). Blood samples were collected before infusion; at the end of infusion; and at 5, 10, 20, 30, 45, 60, 90, and 120 min and 3, 4, 6, 12, 18, 24, 48, and 72 h after infusion. Enoxacin and oxoenoxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters (mean +/- standard deviation) were calculated by using a noncompartmental PK model according to creatinine clearances (in milliliters per minute). Total clearance of enoxacin decreased from 4.95 +/- 1.16 ml/min per kg in the group with normal creatinine clearance to 0.76 +/- 0.21 ml/min per kg in the patients with severe renal failure (creatinine clearance, less than 15 ml/min), whereas the elimination half-life increased from 4.5 +/- 1.0 to 20 +/- 5 h, respectively. The elimination of oxoenoxacin (the main metabolite of enoxacin) in urine was markedly decreased when creatinine clearance was less than 15 ml/min. Hemodialysis removed an insignificant amount of enoxacin and oxoenoxacin. These data indicate that as creatinine clearance falls below 30 ml/min, the daily enoxacin dose should be reduced by half. During prolonged administration of enoxacin to patients with creatinine clearances of less than 30 ml/min, the accumulation of oxoenoxacin might lead to unexpected side effects.
Van der Auwera
P
P
Service de Médecine, Clinique H.J. Tagnon, Institut Jules Bordet, Université Libre de Bruxelles, Belgium.
Stolear
J C
JC
George
B
B
Dudley
M N
MN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000097:blood; D015365:Enoxacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008875:Middle Aged; D006435:Renal Dialysis
D015365:Enoxacin; C049814:4-oxo-enoxacin; D003404:Creatinine