{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T01:15:48Z","timestamp":1783732548531,"version":"3.55.0"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"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":[[2013,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            This study evaluated the pharmacokinetics of topical creams containing 15% paromomycin (\u201cparomomycin alone\u201d) and 15% paromomycin plus 0.5% gentamicin (WR 279,396) in patients with cutaneous leishmaniasis. The investigational creams were applied topically to all lesions once daily for 20 days. Plasma samples were analyzed for simultaneous quantitation of paromomycin and gentamicin isomers and total gentamicin. Pharmacokinetic parameters for gentamicin could not be calculated because detectable levels were rarely evident. After one application, the paromomycin area under the concentration-time curve from 0 to 24 h (AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            ) was 2,180 \u00b1 2,621 ng \u00b7 h\/ml (mean \u00b1 standard deviation [SD]) for the paromomycin-alone group and 975.6 \u00b1 1,078 ng \u00b7 h\/ml for the WR 279,396 group. After 20 days of application, the paromomycin AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            and maximum concentration of drug (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ) were 5 to 6 times greater than those on day 1 for both treatment groups. For the paromomycin-alone group, the AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            was 8,575 \u00b1 7,268 ng \u00b7 h\/ml and the\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            was 1,000 \u00b1 750 ng\/ml, compared with 6,037 \u00b1 3,956 ng \u00b7 h\/ml and 660 \u00b1 486 ng\/ml for the WR 279,396 group, respectively. Possibly due to large intersubject variability, no differences (\n            <jats:italic>P<\/jats:italic>\n            \u2265 0.05) in the AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            or\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            were noted between treatment or between sites on day 1 or 20. The percentage of dose absorbed on day 20 was 12.0% \u00b1 6.26% and 9.68% \u00b1 6.05% for paromomycin alone and WR 279,396, respectively. Paromomycin concentrations in plasma after 20 days of application were 5 to 9% of those after intramuscular administration of 15 mg\/kg of body weight\/day to adults for the systemic treatment of visceral leishmaniasis. Effective topical treatment of cutaneous leishmaniasis appears to be possible with limited paromomycin and gentamicin systemic absorption, thus avoiding drug accumulation and toxicity. (The work described here has been registered at\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n            under registration no. NCT01032382 and NCT01083576.)\n          <\/jats:p>","DOI":"10.1128\/aac.00628-13","type":"journal-article","created":{"date-parts":[[2013,7,23]],"date-time":"2013-07-23T02:15:44Z","timestamp":1374545744000},"page":"4809-4815","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Pharmacokinetics and Absorption of Paromomycin and Gentamicin from Topical Creams Used To Treat Cutaneous Leishmaniasis"],"prefix":"10.1128","volume":"57","author":[{"given":"William R.","family":"Ravis","sequence":"first","affiliation":[{"name":"Auburn University, Auburn, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Llanos-Cuentas","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Tropical, Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nestor","family":"Sosa","sequence":"additional","affiliation":[{"name":"Instituto Conmemorativo Gorgas de Estudios de la Salud, Panama City, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Kreishman-Deitrick","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Materiel Development Activity, Fort Detrick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Kopydlowski","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Materiel Development Activity, Fort Detrick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Nielsen","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Materiel Development Activity, Fort Detrick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten S.","family":"Smith","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Materiel Development Activity, Fort Detrick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"Smith","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Materiel Development Activity, Fort Detrick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet H.","family":"Ransom","sequence":"additional","affiliation":[{"name":"Fast-Track Drugs and Biologics, North Potomac, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuh-Jing","family":"Lin","sequence":"additional","affiliation":[{"name":"Auburn University, Auburn, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Grogl","sequence":"additional","affiliation":[{"name":"Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(07)70209-8"},{"key":"e_1_3_2_3_2","volume-title":"Report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22\u201326 March; WHO Technical Report Series 949","author":"World Health Organization","year":"2010","unstructured":"World Health Organization. 2010. Control of the leishmaniases. Report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22\u201326 March; WHO Technical Report Series 949. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_2_4_2","unstructured":"University of Texas Southwestern Medical Center. 2008. Dermatologists identify North Texas leishmaniasis outbreak. New release Dallas: Sept. 14 2007. University of Texas Southwestern Medical Center Dallas TX. http:\/\/www.utsouthwestern.edu\/utsw\/cda\/dept353744\/files\/411952.html. Accessed 15 August 2012."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2004.06.018"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000313"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2307\/3285646"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/35.5.577"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/374783"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182009990679"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2010.01237.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202657"},{"key":"e_1_3_2_13_2","article-title":"Randomized, double-blinded, phase 2 trial of WR 279,396 (paromomycin and gentamicin) for cutaneous leishmaniasis in Panama","author":"Sosa N","unstructured":"SosaNCapit\u00e1nZNietoJMietoMCalzadaJPazHSpadaforaCKreishman-DeitrickMKopydlowskiKUllmanDMcCarthyWFRansomJHBermanJScottCGroglM. Randomized, double-blinded, phase 2 trial of WR 279,396 (paromomycin and gentamicin) for cutaneous leishmaniasis in Panama. Am. J. Trop. Med. Hyg., in press.","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.982"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1081\/DDC-120030423"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.63.10.692"},{"key":"e_1_3_2_18_2","unstructured":"Institute for One World Health. 2010. Application for inclusion of paromomycin in the WHO Model List of Essential Medicine. Version 12 October 2006. Institute for One World Health San Francisco CA. http:\/\/archives.who.int\/eml\/expcom\/expcom15\/applications\/newmed\/paromomycin\/paromomycin.pdf."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1159\/000074057"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(84)90578-7"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00628-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00628-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:30:42Z","timestamp":1645482642000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00628-13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1128\/AAC.00628-13"],"URL":"https:\/\/doi.org\/10.1128\/aac.00628-13","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10]]},"assertion":[{"value":"2013-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}