Pharmacokinetics of temafloxacin in patients with liver impairment.
A multicentre study was conducted to determine whether liver impairment would alter the pharmacokinetics of temafloxacin, a new fluoroquinolone antimicrobial agent. 16 patients with cirrhosis and 12 healthy volunteers (the control group) received a single oral 600mg dose of temafloxacin. Blood and urine were sampled at frequent intervals after drug administration and assayed by high performance liquid chromatography. The mean age of patients with liver impairment was greater than that of the control group; they also had a lower creatinine clearance and urine output. There was no difference between the groups in either the peak plasma temafloxacin concentration or the time to reach peak concentration. However, the volume of distribution and elimination rate constant of temafloxacin were significantly lower in the group with liver impairment, as were total temafloxacin clearance, renal clearance, and the ratio of renal:creatinine clearance. Nonrenal clearance was similar in patients and controls. Creatinine clearance and urine output were found to account for most of the intersubject variability in total clearance as determined by multiple linear regression analysis. Because the altered temafloxacin pharmacokinetics appear to be primarily due to impaired renal function, this should be the main determinant of temafloxacin dosage in patients with liver disease.
Granneman
G R
GR
IBMP-Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany.
Mahr
G
G
Locke
C
C
Nickel
P
P
Kirch
W
W
Fabian
W
W
Kinzig
M
M
Naber
K G
KG
Sörgel
F
F
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C054745:temafloxacin