The pharmacokinetics of antofloxacin in renally impaired rats.
Our aim was to investigate whether renal impairment induced by cisplatin altered the pharmacokinetics of antofloxacin. Antofloxacin (7.5 mg kg(-1), i.v.) was given to normal or renally impaired rats (induced by cisplatin). Concentrations of antofloxacin in plasma and urine were measured using HPLC. Pharmacokinetic parameters were estimated. The plasma concentrations of antofloxacin in the renally impaired rats were significantly higher than those in the normal rats, accompanied by significant increase of the area under the plasma concentration-time curve (AUC) (968.78+/-259.39 microg min mL(-1) versus 509.84+/-46.19 microg min mL(-1) in normal rats P < 0.05). The system clearance (CL) and renal clearance (CL(R)) of antofloxacin decreased from 12.66+/-1.15 mL kg(-1) min(-1) and 3.21+/-1.80 mL kg(-1) min(-1) in normal rats, to 6.63+/-2.82 mL kg(-1) min(-1) and 0.31+/-0.15 mL kg(-1)min(-1), respectively. No differences between two treatments in half-life and mean residence time were found. We concluded that renal impairment induced by cisplatin significantly altered the pharma-cokinetics of antofloxacin and resulted in decrease of the renal elimination.
Pang
X Y
XY
Jiangsu Key Laboratory for Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, PR China.
Liu
L
L
Zhang
D M
DM
Wang
G J
GJ
Xie
L
L
Liu
X D
XD
D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D002945:Cisplatin; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D015242:Ofloxacin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; C522674:antofloxacin; D015242:Ofloxacin; D002945:Cisplatin