{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:27:40Z","timestamp":1787016460834,"version":"build-2736575974"},"reference-count":12,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2009,6,1]],"date-time":"2009-06-01T00:00:00Z","timestamp":1243814400000},"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":[[2009,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nikkomycin Z is an antifungal drug that inhibits chitin synthase. This agent is under development as an orphan product for treatment of coccidioidomycosis. Safety and pharmacokinetics of nikkomycin Z were evaluated in healthy male subjects following single, rising oral doses ranging from 250 mg to 2,000 mg. A total of 12 subjects were recruited and divided into two groups. Group 1 (\n                    <jats:italic>n<\/jats:italic>\n                    = 6) received two out of three doses of 250 mg, 1,000 mg, or 1,750 mg and a placebo randomly in place of one of the doses. Group 2 (\n                    <jats:italic>n<\/jats:italic>\n                    = 6) received two out of three doses of 500 mg, 1,500 mg, or 2,000 mg and a placebo in place of one of the doses. Subjects were confined to the study unit overnight prior to dosing, and 12 blood samples were collected over 24 h postdosing while subjects were confined. Subjects returned for additional blood samples and safety evaluations at 48 h and 72 h after each dose. There was a 2-week washout period between doses. Plasma drug concentrations were determined using a validated high-performance liquid chromatography method. Nikkomycin Z was absorbed after oral administration, reaching a maximum concentration in serum of 2.21 \u03bcg\/ml at 2 h postdose and an area under the concentration-time curve from 0 h to infinity of 11.3 \u03bcg\u00b7h\/ml for the 250-mg dose. Pharmacokinetics appeared linear over the range of 250 to 500 mg; however, relative bioavailability was about 62 to 70% for the 1,000-mg dose and 42 to 47% for doses between 1,500 and 2,000 mg. The mean terminal half-life ranged from 2.1 to 2.5 h and was independent of dose. No serious or dose-related adverse events were observed. This study provides a basis for pharmacokinetic simulations and continued studies of nikkomycin Z administered in multiple doses.\n                  <\/jats:p>","DOI":"10.1128\/aac.01609-08","type":"journal-article","created":{"date-parts":[[2009,4,6]],"date-time":"2009-04-06T21:07:24Z","timestamp":1239052044000},"page":"2517-2521","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":85,"title":["Pharmacokinetics of Nikkomycin Z after Single Rising Oral Doses"],"prefix":"10.1128","volume":"53","author":[{"given":"David E.","family":"Nix","sequence":"first","affiliation":[{"name":"Valley Fever Center for Excellence, Colleges of Pharmacy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Swezey","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Hector","sequence":"additional","affiliation":[{"name":"University of California San Francisco Institute for Global Health, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Galgiani","sequence":"additional","affiliation":[{"name":"Valley Fever Center for Excellence, Colleges of Pharmacy"},{"name":"Medicine, University of Arizona, Tucson, Arizona"},{"name":"Southern Arizona VA Health Care System, Tucson, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"940","volume":"98","year":"2006","unstructured":"Antony, S. J., P. Jurczyk, and L. Brumble. 2006. Successful use of combination antifungal therapy in the treatment of coccidioides meningitis. J. Nat. Med. Assoc.98:940-942.","journal-title":"J. Nat. Med. Assoc."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.9.2026"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/496991"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.18.5857-5860.1994"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.6.1624-1629.2000"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2371"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.4.587"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/j.1439-0507.2005.01155.x","volume":"48","year":"2005","unstructured":"Herrin, K. V., A. Miranda, and D. Loebenberg. 2005. Posaconazole therapy for systemic coccidioidomycosis in a chimpanzee (Pan troglodytes): a case report. Mycoses48:447-452.","journal-title":"Mycoses"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/S0960-894X(00)00256-0","volume":"10","year":"2000","unstructured":"Obi, K., J. Uda, K. Iwase, O. Sugimoto, H. Ebisu, and A. Matsuda. 2000. Novel nikkomycin analogues: inhibitors of the fungal cell wall biosynthesis enzyme chitin synthase. Bioorg. Med. Chem. Lett.10:1451-1454.","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s11046-007-9018-7","volume":"163","year":"2007","unstructured":"Ramani, R., and V. Chaturvedi. 2007. Antifungal susceptibility profiles of Coccidioides immitis and Coccidioides posadasii from endemic and non-endemic areas. Mycopathalogia163:315-319.","journal-title":"Mycopathalogia"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568005033342064"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026451721686"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01609-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01609-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T18:19:13Z","timestamp":1645467553000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01609-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6]]},"references-count":12,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2009,6]]}},"alternative-id":["10.1128\/AAC.01609-08"],"URL":"https:\/\/doi.org\/10.1128\/aac.01609-08","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6]]},"assertion":[{"value":"2008-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-03-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}