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Multiple dose kinetics of ofloxacin and ofloxacin metabolites in haemodialysis patients

✍ Scribed by D. Kampf; K. Borner; A. Pustelnik


Publisher
Springer
Year
1992
Tongue
English
Weight
424 KB
Volume
42
Category
Article
ISSN
0031-6970

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✦ Synopsis


7 patients with end-stage renal disease on regular haemodialysis were treated orally with a loading dose of 200 mg ofloxacin and multiple maintenance doses of 100 mg per 24 h for 10 days. The pharmacokinetics of ofloxacin and its metabolites were studied at the end of the treatment period. Plasma and dialysate concentrations of ofloxacin and ofloxacin metabolites were measured by HPLC. Peak (3.1 mg.l-1) and trough levels (1.6 mg.l-1) and the AUC of ofloxacin were comparable to the values in healthy volunteers given 300 to 400 mg ofloxacin p.o. The mean half-life, determined in the dialysis-free interval (t1/2 beta) and during the haemodialysis session (t1/2 HD), was 38.5 h and 9.9 h, respectively. Extrarenal clearance (32.7 ml.min-1) was unchanged as compared to that reported in healthy volunteers after a single dose of ofloxacin. The fractional removal by haemodialysis amounted to 21.5%. Two metabolites, ofloxacin-N-oxide and demethyl-ofloxacin, were detected in plasma. Despite prolonged t1/2 beta of both metabolites (66.1 and 50.9 h) and multiple doses of ofloxacin the peak concentrations of the metabolites reached only 14% and 5% of that of the parent drug, respectively. It is concluded that in patients on regular haemodialysis treatment the dosage adjustment employed resulted in safe and therapeutically favourable plasma concentrations. The observed accumulation of ofloxacin metabolites does not appear to have any toxic or therapeutic significance.


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## Abstract The aim of this study was to determine whether the dose influences the distribution kinetics of ciprofloxacin and ofloxacin in muscle‐ bone‐ and skin‐tissues included in the isolated hindlimb of the rat. Experiments were carried out in the isolated perfused hindlimb of the rat, administ