The influence of a newly developed quinolone: antofloxacin, on CYP activity in rats.

Eur J Drug Metab Pharmacokinet

Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, People's Republic of China.

Published: July 2008

To investigate a newly developed quinolone antibiotics, the effect of antofloxacin hydrochloride on cytochrome P450 isoforms in rats was examined. A cocktail approach was adopted. Theophylline (CYP1A2), midazolam (CYP3A), chlorzoxazone (CYP2E1), dextromethorphan (CYP2D6), omeprazole (CYP2C19) and diclofenac (CYP2C9) were used as probes in the study, and own control was adopted. In Protocol 1, probes were given to rats simultaneously by co-administration with antofloxacin. The blood samples were obtained at designated time, and plasma concentrations of the six probes were determined by LC-MS. The pharmacokinetic parameters were calculated and compared in experimental groups in the absence and presence of antofloxacin. The result showed that the presence of antofloxacin resulted in a significant increase in theophylline values of AUC0-T and t1/2 (PAUC0-T = 0.0004 vs control Pt1/2 = 0.005 vs control), indicating that antofloxacin delayed the clearance of theophylline. In Protocol 2, the probes' pharmacokinetic parameters were compared in rats that received six probes before and after 14.5 days of consecutive administration of antofloxacin (15 mg x kg(-1), given orally, twice daily). The results suggested that the AUC0-T of chlorzoxazone was significantly decreased (P = 0.024), while that of dextromethorphan was significantly increased (P = 0.027). In conclusion, these results indicated that antofloxacin may inhibit the activity of CYP1A2, thus delaying the clearance of its substrates, and may have a slight inhibitory effect on CYP2D6 as well as an inductive effect on CYP2E1 following chronic administration.

Download full-text PDF

Source
http://dx.doi.org/10.1007/BF03191012DOI Listing

Publication Analysis

Top Keywords

newly developed
8
developed quinolone
8
antofloxacin
8
pharmacokinetic parameters
8
presence antofloxacin
8
influence newly
4
quinolone antofloxacin
4
antofloxacin cyp
4
cyp activity
4
rats
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!