The pharmacokinetics of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide in haemodialysis patients with end-stage renal failure.
Six patients with end-stage chronic renal failure undergoing haemodialysis were given ofloxacin (600 mg) orally and blood samples were taken at intervals up to 32 h. In four patients samples were also taken before and after haemodialysis. Serum concentrations of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide were measured by HPLC. The drug was well tolerated. Mean pharmacokinetic parameters for ofloxacin were Cmax 5.5 h (S.D. 1.97 h), Tmax 3.9 h (S.D. 3.25 h), T1/2 28 h (S.D. 17.37 h), AUC0-24 83.1 mg/1 h (S.D. 32.69 mg/l h). The desmethyl metabolite was produced in all patients but only half produced N-oxide. Cmax values were 0.21 mg/l (desmethyl) and 0.37 mg/l (N-oxide). Ofloxacin and desmethyl ofloxacin were variably and only slightly removed by haemodialysis whilst ofloxacin N-oxide was not removed at all. These results confirm that dosage reduction of ofloxacin is required in haemodialysis patients. Therapeutic drug monitoring by HPLC is recommended because of the observed variability in absorption and plasma half life.
White
L O
LO
Department of Microbiology, Southmead Hospital, Bristol, UK.
MacGowan
A P
AP
Mackay
I G
IG
Reeves
D S
DS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents; D002851:Chromatography, High Pressure Liquid; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D006435:Renal Dialysis
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; C054988:desmethylofloxacin; C054987:ofloxacin N-oxide; D015242:Ofloxacin