{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T10:00:37Z","timestamp":1777111237713,"version":"3.51.4"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"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":[[2015,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>This study aimed to characterize the stereoselective pharmacokinetics of oral eflornithine in 25 patients with late-stage<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trypanosoma brucei<\/jats:named-content><jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">gambiense<\/jats:named-content>sleeping sickness. A secondary aim was to determine the concentrations of<jats:sc>l<\/jats:sc>- and<jats:sc>d<\/jats:sc>-eflornithine required in plasma or cerebrospinal fluid (CSF) for an efficient eradication of the<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. brucei gambiense<\/jats:named-content>parasites. Patients were randomly allocated to receive either 100 (group I,<jats:italic>n<\/jats:italic>= 12) or 125 (group II,<jats:italic>n<\/jats:italic>= 13) mg\/kg of body weight of drug every 6 h for 14 days. The concentrations of<jats:sc>l<\/jats:sc>- and<jats:sc>d<\/jats:sc>-eflornithine in the plasma and CSF samples were measured using a stereospecific liquid chromatographic method. Nonlinear mixed-effects modeling was used to characterize the plasma pharmacokinetics. The plasma concentrations of<jats:sc>l<\/jats:sc>-eflornithine were on average 52% (95% confidence interval [CI], 51, 54%;<jats:italic>n<\/jats:italic>= 321) of the<jats:sc>d<\/jats:sc>-enantiomer concentrations. The typical oral clearances of<jats:sc>l<\/jats:sc>- and<jats:sc>d<\/jats:sc>-eflornithine were 17.4 (95% CI, 15.5, 19.3) and 8.23 (95% CI, 7.36, 9.10) liters\/h, respectively. These differences were likely due to stereoselective intestinal absorption. The distributions of eflornithine enantiomers to the CSF were not stereoselective. A correlation was found between the probability of cure and plasma drug exposure, although it was not more pronounced for the<jats:sc>l<\/jats:sc>-enantiomer than for that of total eflornithine. This study may explain why oral treatment for late-stage human African trypanosomiasis (HAT) patients with racemic eflornithine has previously failed; the more potent<jats:sc>l<\/jats:sc>-enantiomer is present at much lower concentrations in both plasma and CSF than those of the<jats:sc>d<\/jats:sc>-enantiomer. Eflornithine stereoselective pharmacokinetics needs to be considered if an oral dosage regimen is to be explored further.<\/jats:p>","DOI":"10.1128\/aac.04101-14","type":"journal-article","created":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T03:19:23Z","timestamp":1418699963000},"page":"1299-1307","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Enantiospecific Reassessment of the Pharmacokinetics and Pharmacodynamics of Oral Eflornithine against Late-Stage Trypanosoma brucei gambiense Sleeping Sickness"],"prefix":"10.1128","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1773-197X","authenticated-orcid":false,"given":"R.","family":"Jansson-L\u00f6fmark","sequence":"first","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"},{"name":"CVMD iMed DMPK, AstraZeneca R&amp;D, M\u00f6lndal, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Na-Bangchang","sequence":"additional","affiliation":[{"name":"Thammasat University, Faculty of Allied Health Sciences, Krung Thep Maha Nakhon, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Bj\u00f6rkman","sequence":"additional","affiliation":[{"name":"Uppsala University, Department of Pharmaceutical Biosciences, Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Doua","sequence":"additional","affiliation":[{"name":"Project de Recherches Cliniques sue la Trypanosomiasie PRCT, B.P. 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