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Evidence of a flip‐flop phenomenon in acamprosate pharmacokinetics: an in vivo study in rats
Author(s) -
Zornoza T.,
CanoCebrián M. J.,
Hipólito L.,
Granero L.,
Polache A.
Publication year - 2006
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.513
Subject(s) - pharmacokinetics , acamprosate , bioavailability , pharmacology , oral administration , absorption (acoustics) , in vivo , elimination rate constant , chemistry , crossover study , medicine , volume of distribution , antagonist , materials science , biology , pathology , naltrexone , receptor , microbiology and biotechnology , composite material , alternative medicine , placebo
The pharmacokinetics of acamprosate were examined in the rat after oral and intravenous administration in order to detect the possible presence of a flip‐flop phenomenon. Rats received 9.3 or 73.3 mg/kg of the drug as an intravenous bolus. The same doses were orally administered via gastric intubation. Plasma samples were taken from the jugular vein for determination of acamprosate concentration by liquid scintillation counting. The drug content was also quantified in urine and faeces. The acamprosate bioavailability was close to 20%, the amount recovered in the faeces being around 80% of the administered dose. The terminal slope of the oral plasma curve was significantly lower than that obtained after intravenous administration of the drug at both doses tested ( p <2 × 10 −6 in both cases). Moreover, the downward slope after oral administration (λ 2 =0.006 ± 0.001 min −1 ) practically coincided with the first‐order absorption rate constant, previously reported by us, obtained using an in situ rat gut technique. It is concluded that the acamprosate absorption rate is considerably slower than its elimination rate so that the drug exhibits flip‐flop pharmacokinetics after oral administration. The lower intrinsic first‐order absorption rate constant, k a , is responsible for this phenomenon. Copyright © 2006 John Wiley & Sons, Ltd.