{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:43:05Z","timestamp":1774690985523,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,10,5]],"date-time":"2005-10-05T00:00:00Z","timestamp":1128470400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2005,10]]},"abstract":"<jats:p>This study was undertaken to characterize the population pharmacokinetics (PK), therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty\u2010three African (<jats:italic>Loxodonta africana<\/jats:italic>) and Asian (<jats:italic>Elephas maximus<\/jats:italic>) elephants infected with or in contact with others culture positive for <jats:italic>Mycobacterium tuberculosis<\/jats:italic> were dosed under treatment conditions. PZA was dosed daily at 20\u201330\u2003mg\/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0\u201324\u2003h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with <jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub> at or before 2\u2003h regardless of the method of drug administration. <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> at a mean dose of 25.6 (\u00b14.6) mg\/kg was 19.6 (\u00b19.5\u2003<jats:italic>\u03bc<\/jats:italic>g\/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1\u2003\u00b1\u20034.2\u2003mg\/kg, <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> was 25% (4.87\u2003\u00b1\u20034.89\u2003<jats:italic>\u03bc<\/jats:italic>g\/mL) and area under concentration curve (<jats:italic>AUC<\/jats:italic>) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6\u2003\u00b1\u200315.2\u2003mg\/kg yielded <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> of 12.3\u2003\u00b1\u20036.3\u2003<jats:italic>\u03bc<\/jats:italic>g\/mL, but comparable <jats:italic>AUC<\/jats:italic> to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> and lower inter\u2010subject variability. A starting dose of 30\u2003mg\/kg is recommended with drug monitoring between 1 and 2\u2003h postdose. Higher doses may be required if the achieved <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> values are below the recommended 20\u201350\u2003<jats:italic>\u03bc<\/jats:italic>g\/mL range.<\/jats:p>","DOI":"10.1111\/j.1365-2885.2005.00670.x","type":"journal-article","created":{"date-parts":[[2005,10,5]],"date-time":"2005-10-05T12:24:36Z","timestamp":1128515076000},"page":"403-409","source":"Crossref","is-referenced-by-count":19,"title":["Population pharmacokinetics of pyrazinamide in elephants"],"prefix":"10.1111","volume":"28","author":[{"given":"M.","family":"ZHU","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. N.","family":"MASLOW","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. K.","family":"MIKOTA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"ISAZA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"DUNKER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"RIDDLE","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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