{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:07:40Z","timestamp":1776769660749,"version":"3.51.2"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2006,6,23]],"date-time":"2006-06-23T00:00:00Z","timestamp":1151020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The pharmacokinetics of acamprosate were examined in the rat after oral and intravenous administration in order to detect the possible presence of a flip\u2010flop 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 (<jats:italic>p<\/jats:italic>&lt;2 \u00d7 10<jats:sup>\u22126<\/jats:sup> in both cases). Moreover, the downward slope after oral administration (\u03bb<jats:sub>2<\/jats:sub>=0.006 \u00b1 0.001 min<jats:sup>\u22121<\/jats:sup>) practically coincided with the first\u2010order absorption rate constant, previously reported by us, obtained using an <jats:italic>in situ<\/jats:italic> rat gut technique. It is concluded that the acamprosate absorption rate is considerably slower than its elimination rate so that the drug exhibits flip\u2010flop pharmacokinetics after oral administration. The lower intrinsic first\u2010order absorption rate constant, <jats:italic>k<\/jats:italic><jats:sub>a<\/jats:sub>, is responsible for this phenomenon. Copyright \u00a9 2006 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.513","type":"journal-article","created":{"date-parts":[[2006,6,27]],"date-time":"2006-06-27T10:49:16Z","timestamp":1151405356000},"page":"305-311","source":"Crossref","is-referenced-by-count":21,"title":["Evidence of a flip\u2010flop phenomenon in acamprosate pharmacokinetics: an <i>in vivo<\/i> study in rats"],"prefix":"10.1002","volume":"27","author":[{"given":"T.","family":"Zornoza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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