Kinetics of 4-fluoroquinolones permeation into saliva.
Following a single oral administration of ciprofloxacin, norfloxacin, pefloxacin and ofloxacin preparations to healthy volunteers simultaneously collected, saliva and plasma 4-fluoroquinolone concentrations were assayed by HPLC. Pharmacokinetic properties were determined by ordinary least squares fitting of the two compartment pharmacokinetic model to the experimental data. A good correlation between plasma and saliva data has been demonstrated. The saliva to venous plasma drug concentration ratio S/P appeared to be time-dependent in the case of norfloxacin and pefloxacin. It was demonstrated that S/P is a function of the quotient of the rate of absorption and venous plasma drug concentration. The calculated S/P ratios with the influence of absorption eliminated, (S/P)(corr) are: ciprofloxacin 0.53+/-0.02, norfloxacin 0.34+/-0.04, ofloxacin 0. 43+/-0.02 and pefloxacin 0.39+/-0.02 (mean+/-S.E.). These values are apparently independent of log D thus making it impossible to predict S/P on the basis of partition principles. The corresponding (S/P)(dif) ratios were calculated on the basis of the assumption that an equilibrium is established across the blood-saliva barrier, which is permeable only for nonionized and nonprotein bound drug fraction. Comparing (S/P)(corr) with the calculated (S/P)(dif) ratios it is evident that 4-fluoroquinolone permeation in saliva cannot be described by passive diffusion based on pH-partition theory.
Kozjek
F
F
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia. franc.kozjek@ffa.uni-lj.si
Suturkova
L J
LJ
Antolic
G
G
Grabnar
I
I
Mrhar
A
A
D000328:Adult; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D008297:Male; D009643:Norfloxacin / Q000097:blood / Q000493:pharmacokinetics; D015242:Ofloxacin / Q000097:blood / Q000493:pharmacokinetics; D015366:Pefloxacin / Q000097:blood / Q000493:pharmacokinetics; D012463:Saliva / Q000378:metabolism*
D000890:Anti-Infective Agents; D015366:Pefloxacin; D002939:Ciprofloxacin; D015242:Ofloxacin; D009643:Norfloxacin