Journal of Antimicrobial Chemotherapy (1990) 26, Suppl. B, 51-60
Pharmacokinetics of quinolones in renal insufficiency J. P. Fiflastre", A. Leroy4, B. Moulin*, M. Dhlb', F. Borsa-Lebas' and G. Humbert1
Departments of "Nephrology, bBiochemistry and 'Infections Diseases, CHU Rouen, France
Introduction
The new fluoroquinolone derivatives are characterized by a broad antibacterial spectrum and are now widely used in the treatment of systemic and urinary tract infections. The pharmacokinetics of these drugs have been extensively studied. They exhibit excellent oral bioavailability (except norfloxacin), extensive tissue diffusion with high volumes of distribution ( > 1-5 I/kg), low protein-binding ( < 30%) and a long elimination half-life (from 3-5 h for ciprofloxacin to 8-14 h for pefloxacin). These new drugs differ in their degree of metabolic biotransformation: high for pefloxacin and very low for ofloxacin and lomefloxacin. Most of them are eliminated essentially via the renal route (30-60%) but also, to some extent by extrarenal pathways. Thus, their pharmacokinetic profiles have been found to be different in patients with renal insufficiency. This paper is a review of the literature on the pharmacokinetics of seven new quinolones—pefloxacin, ciprofloxacin, enoxacin, norfloxacin, fleroxacin, ofloxacin and lomefloxacin—in subjects with different degrees of chronic renal impairment. Methods used
Many pharmacokinetic studies were performed in different groups of patients with mild, moderate and severe renal insufficiency after single oral and/or iv doses of the drug. In most studies, plasma and urine concentrations of the unchanged drug and metabolites were measured by HPLC assay. From the pharmacokinetic results and the Corresponding author Professor J. P. Fillartre, Department of Nephrology, H dpi la] de Bob Guillaume, Avenue du Marechal Juin, 76230 Bois Guillaurae, France. 0305-7453/90/26B051 + 10 $02.00/0
51 © 1990 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at Boston University on September 15, 2014
The pharmacokinetics of the new fluoroquinolone derivatives have been extensively studied in patients with various degrees of chronic renal insufficiency during the last few years. Their kinetic profiles depend on the elimination pathways and on the degree of metabolic transformation. Renal insufficiency does not significantly modify pefloxacin kinetics. For the other new quinolones, a decrease in glomerular filtration rate below 20-30 ml/min induces an increase in terminal half-life and a decrease in plasma and renal clearance, related to the degree of renal impairment. These drugs are poorly removed by haemodialysis. Dosage adjustments are required, particularly in severe renal failure and for the drugs almost exclusively excreted, in unchanged form, via the renal route.
52
J. P. FUlastre et al
bacteriological data, dosage adjustments were proposed according to the degree of renal failure. Pefloxacin
Table L Pharmacokinetic parameters of pefloxacin in uraemic patients after a single iv dose, as 1 h-infusion Normal renal function GFR (ml/min) Dose C«x (mg/1) ^dO/kg) 7\(h) C\ (ml/min) Cl, (ml/min)
>80 600 mg iv 6-6-5 1-57 ±0-26 12±2 127±31 15±7
Barre el al.. 1984; Montay el al., 1985.
Renal impairment moderate severe 10-50
< 10 8 mg/kg iv 5-7 ±0-4 5-3 ±05 l-98±0-13 2O7±0-18 15±2 12±2 109±14 132±13
Pharmacokinetics of quinolones in renal insufficiency J. P. Fiflastre", A. Leroy4, B. Moulin*, M. Dhlb', F. Borsa-Lebas' and G. Humbert1
Departments of "Nephrology, bBiochemistry and 'Infections Diseases, CHU Rouen, France
Introduction
The new fluoroquinolone derivatives are characterized by a broad antibacterial spectrum and are now widely used in the treatment of systemic and urinary tract infections. The pharmacokinetics of these drugs have been extensively studied. They exhibit excellent oral bioavailability (except norfloxacin), extensive tissue diffusion with high volumes of distribution ( > 1-5 I/kg), low protein-binding ( < 30%) and a long elimination half-life (from 3-5 h for ciprofloxacin to 8-14 h for pefloxacin). These new drugs differ in their degree of metabolic biotransformation: high for pefloxacin and very low for ofloxacin and lomefloxacin. Most of them are eliminated essentially via the renal route (30-60%) but also, to some extent by extrarenal pathways. Thus, their pharmacokinetic profiles have been found to be different in patients with renal insufficiency. This paper is a review of the literature on the pharmacokinetics of seven new quinolones—pefloxacin, ciprofloxacin, enoxacin, norfloxacin, fleroxacin, ofloxacin and lomefloxacin—in subjects with different degrees of chronic renal impairment. Methods used
Many pharmacokinetic studies were performed in different groups of patients with mild, moderate and severe renal insufficiency after single oral and/or iv doses of the drug. In most studies, plasma and urine concentrations of the unchanged drug and metabolites were measured by HPLC assay. From the pharmacokinetic results and the Corresponding author Professor J. P. Fillartre, Department of Nephrology, H dpi la] de Bob Guillaume, Avenue du Marechal Juin, 76230 Bois Guillaurae, France. 0305-7453/90/26B051 + 10 $02.00/0
51 © 1990 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at Boston University on September 15, 2014
The pharmacokinetics of the new fluoroquinolone derivatives have been extensively studied in patients with various degrees of chronic renal insufficiency during the last few years. Their kinetic profiles depend on the elimination pathways and on the degree of metabolic transformation. Renal insufficiency does not significantly modify pefloxacin kinetics. For the other new quinolones, a decrease in glomerular filtration rate below 20-30 ml/min induces an increase in terminal half-life and a decrease in plasma and renal clearance, related to the degree of renal impairment. These drugs are poorly removed by haemodialysis. Dosage adjustments are required, particularly in severe renal failure and for the drugs almost exclusively excreted, in unchanged form, via the renal route.
52
J. P. FUlastre et al
bacteriological data, dosage adjustments were proposed according to the degree of renal failure. Pefloxacin
Table L Pharmacokinetic parameters of pefloxacin in uraemic patients after a single iv dose, as 1 h-infusion Normal renal function GFR (ml/min) Dose C«x (mg/1) ^dO/kg) 7\(h) C\ (ml/min) Cl, (ml/min)
>80 600 mg iv 6-6-5 1-57 ±0-26 12±2 127±31 15±7
Barre el al.. 1984; Montay el al., 1985.
Renal impairment moderate severe 10-50
< 10 8 mg/kg iv 5-7 ±0-4 5-3 ±05 l-98±0-13 2O7±0-18 15±2 12±2 109±14 132±13
