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Effect of ofloxacin on theophylline pharmacokinetics at clinical dosage in dogs
Author(s) -
REGMI N. L.,
ABD ELATY A. M.,
KUBOTA R.,
TOMITA A.,
SHIMODA M.
Publication year - 2006
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2006.00784.x
Subject(s) - theophylline , pharmacokinetics , chemistry , ofloxacin , pharmacology , norfloxacin , antibiotics , medicine , biochemistry , ciprofloxacin
We examined the effects of ofloxacin (OFX) and norfloxacin (NFX) on theophylline (TP) pharmacokinetics in dogs. OFX, as a noncompetitive and mechanism‐based inhibitor, and NFX, as a noncompetitive inhibitor, were orally administered (5 mg/kg) for a single dose or multiple doses (12 hourly for 3 days). TP (5 mg/kg, i.v) was injected at 2 h after the final dose of the fluoroquinolones (FQs). The same dose of TP was injected (i.v) 3 weeks before the start of FQs treatment for control. Multiple doses of OFX significantly reduced the total body clearance ( Cl B ) of TP from 0.117 to 0.085 L/h/kg, although a single dose did not change it. Neither a single dose nor multiple doses of NFX changed the TP pharmacokinetics. Plasma NFX concentrations increased after multiple doses. Those of OFX also increased but were still two orders of magnitude below the K i for noncompetitive inhibition of CYP1A in dogs. Time‐dependent reduction in Cl B of TP suggests that mechanism‐based inhibition of OFX was the major mode to decrease Cl B of TP. The mechanism‐based inhibition may result in substantial inhibition of CYP1A activities in clinical conditions.