Pharmacokinetics of Lomefloxacin Patients with Cirrhosis DIDIER
LEBREC,
M.D.,
CHRISTOPHE
GAUDIN,
M.D., JEAN-PIERRE
BENHAMOU,
The effect of liver failure on the pharmacokinetics of lomefloxacin was studied in 12 patients with cirrhosis. Patients received a single oral dose of 400 mg lomefloxacin, and blood and urine samples were collected at intervals over the next 48 hours. The concentrations of lomefloxacin in all samples were measured using high-pressure liquid chromatography (HPLC). The mean (+ standard deviation) maximum plasma concentration (C,,,) in these patients was 3.9 k 1.20 pg/mL. The mean time to maximum serum concentration (T,,,) was 2.1 + 2.6 hours, and the mean elimination half-life (t,,J was 9.16 of: 1.93 hours. Mean renal clearance was 88.9 f 38.0 mWminA.73 m’, and the mean nonrenal clearance was 61.6 f 19.0 mL/min/1.73 m’, wh‘ich corresponded to 41% of the total body clearance. No correlations were observed between nonrenal clearance and hepatic insufficiency (Pugh score) or nonrenal clearance and plasma bilirubin. These results show thtit liver failure does not per se affect lomefloxacin kinetics. Thus, no adjustments in lomefloxacin dosages appear to be necessary for patients with impaired liver function tests.
de Physlopathologie
HBpatique (INSERM U-24) and Service d’Hepatologle,
Requests for reprints should be addressed to Dldier Lebrec. M.D., INSERM
in M.D.,
cm~y, France
L
omefloxacin is a new difluorinated quinolone antimicrobial agent that has been demonstrated to have a broad antibacterial spectrum [l31. Such an anti-infective agent could be useful in patients with liver diseases who have respiratory tract infections or urinary tract infections. The purpose of this study was to determine the effects of liver failure on the pharmacokinetics of lomefloxacin.
PATIENTSAND METHODS Patients Twelve adult patients with histologically proven cirrhosis were enrolled in this study. Mean clinical and laboratory data for these patients are given in Table I. The degree of severity of liver disease was evaluated in all patients using Pugh’s classification [4]. Concomitant treatments, including diuretics, were stopped at least 48 hours before the beginning of the study. The study was approved by the Cornit d’Ethique de la Facultk de Medecine Xavier Bichat. All patients gave written informed consent for the investigations described in this article. Study Protocol After an overnight fast, all patients received a single oral dose of 400 mg lomefloxacin in the form of two 200 mg capsules. Blood samples (7 mL) were collected in lithium heparinate-containing tubes prior to administration and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 10, 24, and 48 hours after administration. Centrifugation was performed ~30 minutes after blood collection, and plasma samples were then stored frozen at -20°C untii lomefloxacin assay. Urine was collected within 2 hours before drug administration and during intervals O-10 hours, lo-24 hours, and 24-48 hours after dosing. Volumes of diuresis were noted, and an aliquot of urine from each collection period was kept frozen at -20°C until lomefloxacin asgay. Adverse reactions were registered. Lomefloxacin Assay Plasma and urine lomefloxacin were determined by high-pressure tography (HPLC) [53.
April 6, 1992
The American Journal of Medicine
concentrations liquid chroma-
Volume 92 (suppl 4A)
4A-41S
SYMPOSIUM
ON ONCE-A-DAY
QUINOLONE
I LEBREC ET AL
r TABLE I Demographic, Clinical, and Laboratory Data for Patients with Cirrhosis Meanf SD
n 6) Sex Male Female Age (years) Weight (kg)
5 (41.7)
7 (58.3) 52rt 12 64 2?14
pp
126 80 +_ 2 35 52 52 +_31 33.92 5.4 4at 10
Bilirubin bmolll) Albumrn (g/L) PT (%of control) Pughscore Creatinme clearance (mUmin/1.73 m2)
9+2
1
.~
78.4? 23.4
._
ALAT = alanmine aminotransferase, normal value
LEBREC,
M.D.,
CHRISTOPHE
GAUDIN,
M.D., JEAN-PIERRE
BENHAMOU,
The effect of liver failure on the pharmacokinetics of lomefloxacin was studied in 12 patients with cirrhosis. Patients received a single oral dose of 400 mg lomefloxacin, and blood and urine samples were collected at intervals over the next 48 hours. The concentrations of lomefloxacin in all samples were measured using high-pressure liquid chromatography (HPLC). The mean (+ standard deviation) maximum plasma concentration (C,,,) in these patients was 3.9 k 1.20 pg/mL. The mean time to maximum serum concentration (T,,,) was 2.1 + 2.6 hours, and the mean elimination half-life (t,,J was 9.16 of: 1.93 hours. Mean renal clearance was 88.9 f 38.0 mWminA.73 m’, and the mean nonrenal clearance was 61.6 f 19.0 mL/min/1.73 m’, wh‘ich corresponded to 41% of the total body clearance. No correlations were observed between nonrenal clearance and hepatic insufficiency (Pugh score) or nonrenal clearance and plasma bilirubin. These results show thtit liver failure does not per se affect lomefloxacin kinetics. Thus, no adjustments in lomefloxacin dosages appear to be necessary for patients with impaired liver function tests.
de Physlopathologie
HBpatique (INSERM U-24) and Service d’Hepatologle,
Requests for reprints should be addressed to Dldier Lebrec. M.D., INSERM
in M.D.,
cm~y, France
L
omefloxacin is a new difluorinated quinolone antimicrobial agent that has been demonstrated to have a broad antibacterial spectrum [l31. Such an anti-infective agent could be useful in patients with liver diseases who have respiratory tract infections or urinary tract infections. The purpose of this study was to determine the effects of liver failure on the pharmacokinetics of lomefloxacin.
PATIENTSAND METHODS Patients Twelve adult patients with histologically proven cirrhosis were enrolled in this study. Mean clinical and laboratory data for these patients are given in Table I. The degree of severity of liver disease was evaluated in all patients using Pugh’s classification [4]. Concomitant treatments, including diuretics, were stopped at least 48 hours before the beginning of the study. The study was approved by the Cornit d’Ethique de la Facultk de Medecine Xavier Bichat. All patients gave written informed consent for the investigations described in this article. Study Protocol After an overnight fast, all patients received a single oral dose of 400 mg lomefloxacin in the form of two 200 mg capsules. Blood samples (7 mL) were collected in lithium heparinate-containing tubes prior to administration and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 10, 24, and 48 hours after administration. Centrifugation was performed ~30 minutes after blood collection, and plasma samples were then stored frozen at -20°C untii lomefloxacin assay. Urine was collected within 2 hours before drug administration and during intervals O-10 hours, lo-24 hours, and 24-48 hours after dosing. Volumes of diuresis were noted, and an aliquot of urine from each collection period was kept frozen at -20°C until lomefloxacin asgay. Adverse reactions were registered. Lomefloxacin Assay Plasma and urine lomefloxacin were determined by high-pressure tography (HPLC) [53.
April 6, 1992
The American Journal of Medicine
concentrations liquid chroma-
Volume 92 (suppl 4A)
4A-41S
SYMPOSIUM
ON ONCE-A-DAY
QUINOLONE
I LEBREC ET AL
r TABLE I Demographic, Clinical, and Laboratory Data for Patients with Cirrhosis Meanf SD
n 6) Sex Male Female Age (years) Weight (kg)
5 (41.7)
7 (58.3) 52rt 12 64 2?14
pp
126 80 +_ 2 35 52 52 +_31 33.92 5.4 4at 10
Bilirubin bmolll) Albumrn (g/L) PT (%of control) Pughscore Creatinme clearance (mUmin/1.73 m2)
9+2
1
.~
78.4? 23.4
._
ALAT = alanmine aminotransferase, normal value
