{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:17:14Z","timestamp":1788398234964,"version":"build-2803163510"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>This study aimed to investigate if the absorption of the human African trypanosomiasis agent eflornithine was stereospecific and dose dependent after oral administration. Male Sprague-Dawley rats were administered single doses of racemic eflornithine hydrochloride as an oral solution (750, 1,500, 2,000, or 3,000 mg\/kg of body weight) or intravenously (375 or 1,000 mg\/kg of body weight). Sparse blood samples were obtained for determination of eflornithine enantiomers by liquid chromatography with evaporative light-scattering detection (lower limit of quantification [LLOQ], 83 \u03bcM for 300 \u03bcl plasma). The full plasma concentration-time profile of racemic eflornithine following frequent sampling was determined for another group of rats, using a high-performance liquid chromatography-UV method (LLOQ, 5 \u03bcM for 50 \u03bcl plasma). Pharmacokinetic data were analyzed in NONMEM for the combined racemic and enantiomeric concentrations. Upon intravenous administration, the plasma concentration-time profile of eflornithine was biphasic, with marginal differences in enantiomer kinetics (mean clearances of 14.5 and 12.6 ml\/min\/kg for<jats:sc>l<\/jats:sc>- and<jats:sc>d<\/jats:sc>-eflornithine, respectively). The complex absorption kinetics were modeled with a number of transit compartments to account for delayed absorption, transferring the drug into an absorption compartment from which the rate of influx was saturable. The mean bioavailabilities for<jats:sc>l<\/jats:sc>- and<jats:sc>d<\/jats:sc>-eflornithine were 41% and 62%, respectively, in the dose range of 750 to 2,000 mg\/kg of body weight, with suggested increases to 47% and 83%, respectively, after a dose of 3,000 mg\/kg of body weight. Eflornithine exhibited enantioselective absorption, with the more potent<jats:sc>l<\/jats:sc>-isomer being less favored, a finding which may help to explain why clinical attempts to develop an oral treatment have hitherto failed. The mechanistic explanation for the stereoselective absorption remains unclear.<\/jats:p>","DOI":"10.1128\/aac.00050-08","type":"journal-article","created":{"date-parts":[[2008,6,3]],"date-time":"2008-06-03T00:58:18Z","timestamp":1212454698000},"page":"2842-2848","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Enantioselective and Nonlinear Intestinal Absorption of Eflornithine in the Rat"],"prefix":"10.1128","volume":"52","author":[{"given":"R.","family":"Jansson","sequence":"first","affiliation":[{"name":"Sahlgrenska Academy at Go\u0308teborg University, Unit for Pharmacokinetics and Drug Metabolism, Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Malm","sequence":"additional","affiliation":[{"name":"Dalarna University College, Borla\u0308nge, Sweden"},{"name":"Department of Physical and Analytical Chemistry, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Roth","sequence":"additional","affiliation":[{"name":"Sahlgrenska Academy at Go\u0308teborg University, Unit for Pharmacokinetics and Drug Metabolism, Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Sahlgrenska Academy at Go\u0308teborg University, Unit for Pharmacokinetics and Drug Metabolism, Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"71","volume":"81","year":"2006","unstructured":"Anonymous. 2006. 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