{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:57:52Z","timestamp":1761490672644},"reference-count":0,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[1996,12,1]],"date-time":"1996-12-01T00:00:00Z","timestamp":849398400000},"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":[[1996,12]]},"abstract":"<jats:p>The pharmacokinetics of 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl) benzoxazinorifamycin (KRM-1648) in rats and dogs given a single oral dose of 3, 30, or 100 mg\/kg of body weight were studied. In the rats, the concentrations of KRM-1648 in plasma, whole blood, and tissues peaked between 2.0 and 24.0 h, with elimination half-lives ranging from 6.2 to 19.5 h. The peak concentrations and the areas under the concentration-versus-time curves (AUC) for whole blood and tissues were 2 to 277 times higher than those for plasma. The high levels of KRM-1648 in tissues were consistent with its large volume of distribution (in excess of 10 liters\/kg). A nonlinear increase in peak concentrations and AUCs for plasma, whole blood, and tissues occurred as the dose was increased and was consistent with the dose-dependent decrease in bioavailability. In the dogs, KRM-1648 levels in plasma and whole blood also exhibited a late time to the peak concentration (ranging from 4.0 to 11.2 h), a long elimination half-life (ranging from 15.2 to 24.0 h), and nonlinear kinetics. KRM-1648 exhibited high levels of plasma protein binding (more than 99%) and a high degree of affinity for lipoproteins in the plasma of both animals. After administration of KRM-1648, measurable levels of its metabolites, 25-deacetyl KRM-1648 in rats and 25-deacetyl KRM-1648 and 30-hydroxy KRM-1648 in dogs, were found in the biological samples tested. Thus, KRM-1648 is characterized by a high tissue affinity, a long elimination half-life, and nonlinear pharmacokinetics.<\/jats:p>","DOI":"10.1128\/aac.40.12.2749","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:24:25Z","timestamp":1539044665000},"page":"2749-2755","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Pharmacokinetics of KRM-1648, a new benzoxazinorifamycin, in rats and dogs"],"prefix":"10.1128","volume":"40","author":[{"given":"K","family":"Hosoe","sequence":"first","affiliation":[{"name":"Takasago Research Laboratory, Hyogo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Mae","sequence":"additional","affiliation":[{"name":"Takasago Research Laboratory, Hyogo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Konishi","sequence":"additional","affiliation":[{"name":"Takasago Research Laboratory, Hyogo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Fujii","sequence":"additional","affiliation":[{"name":"Takasago Research Laboratory, Hyogo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Takasago Research Laboratory, Hyogo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Yamane","sequence":"additional","affiliation":[{"name":"Takasago Research Laboratory, Hyogo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Hidaka","sequence":"additional","affiliation":[{"name":"Takasago Research Laboratory, Hyogo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Takasago Research Laboratory, Hyogo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.40.12.2749","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.40.12.2749","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:03:23Z","timestamp":1645473803000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.40.12.2749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,12]]},"references-count":0,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1996,12]]}},"alternative-id":["10.1128\/AAC.40.12.2749"],"URL":"https:\/\/doi.org\/10.1128\/aac.40.12.2749","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,12]]},"assertion":[{"value":"1996-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}