The pharmacokinetics of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide in haemodialysis patients with end-stage renal failure

Abstract

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.

Enantioselective disposition of ofloxacin in humans

“…Many pharmacokinetic parameters of OFLX have been established in healthy (11) and renal failure (25) subjects. The present data show that concentration profiles of S-(-)-OFLX and R-(+)-OFLX in serum after oral (±)-OFLX administration in humans were almost equal to those of the racemic drug reported in healthy subjects.…”

“…However, there exist species differences in OFLX glucuronidation, as the small amount of glucuronide excreted in urine by dogs and monkeys indicates (19). In humans, (±)-OFLX has been shown to undergo only limited metabolism with urinary excretion of small amounts of metabolites (desmethyl OFLX and OFLX N-oxide) and most of the administered drug is excreted unchanged in the urine (11,24,25).…”

Ofloxacin Clinical Pharmacokinetics

“…Demethyl-ofloxacin has moderate antibacterial activity and can represent 39 2 to 20% of ofloxacin concentrations. Such low metabolite concentrations are present even in renal failure that it is of negligible clinical importance (White et al 1987(White et al , 1988.…”

Effects of traditional Chinese medicines on pharmacokinetics of levofloxacin

“…The apparent t 1/2 values (approximately 8 h) for LVFX were also nearly equal to the values for healthy volunteers (1,13) and those for patients with human immunodeficiency virus infections (4). It has been reported that a small amount of ofloxacin is metabolized (10,17,18). In this study, for all treatment groups the percentages of LVFX recovered from urine within 24 h ranged from 80 to 90%, results identical to data in the review by Davis and Bryson (1) and indicating that the total systemic availabilities of LVFX for the four doses are nearly equal.…”