A preliminary study of the plasma concentrations of orally administered fluconazole in alpacas (Vicugna pacos)
Alpacas residing in the region endemic for Coccidioides spp. are susceptible to serious, disseminated coccidioidomycosis that may result in death. There is currently no oral antifungal dose recommendation for this species. We used a steady‐state study design to assess the pharmacokinetics of oral ge...
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Veröffentlicht in: | Journal of veterinary pharmacology and therapeutics 2022-01, Vol.45 (1), p.99-106 |
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description | Alpacas residing in the region endemic for Coccidioides spp. are susceptible to serious, disseminated coccidioidomycosis that may result in death. There is currently no oral antifungal dose recommendation for this species. We used a steady‐state study design to assess the pharmacokinetics of oral generic fluconazole in alpacas dosed q 24 h for 14 days. Cohorts of 2–3 animals received fluconazole from 6 to 15 mg/kg/day, and pharmacokinetic analysis was performed after each group of animals in order to make dose adjustments for the next group. The final three animals were used as confirmation of our dose recommendation. The median Tmax was 7 h, and the median Cmax was 1.25 µg/ml per mg/kg dose. The mean dose‐normalized 24‐h AUC was 41.7 µg h/ml per mg/kg dose (CV = 72%). Based on these results, we recommend alpacas receive a starting dose of oral fluconazole at 10–15 mg/kg/day based on the fluconazole AUC in humans (313–625 µg h/ml). Testing to ascertain putative therapeutic plasma concentrations and monitoring of serum transaminases should be performed. |
doi_str_mv | 10.1111/jvp.12994 |
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There is currently no oral antifungal dose recommendation for this species. We used a steady‐state study design to assess the pharmacokinetics of oral generic fluconazole in alpacas dosed q 24 h for 14 days. Cohorts of 2–3 animals received fluconazole from 6 to 15 mg/kg/day, and pharmacokinetic analysis was performed after each group of animals in order to make dose adjustments for the next group. The final three animals were used as confirmation of our dose recommendation. The median Tmax was 7 h, and the median Cmax was 1.25 µg/ml per mg/kg dose. The mean dose‐normalized 24‐h AUC was 41.7 µg h/ml per mg/kg dose (CV = 72%). Based on these results, we recommend alpacas receive a starting dose of oral fluconazole at 10–15 mg/kg/day based on the fluconazole AUC in humans (313–625 µg h/ml). Testing to ascertain putative therapeutic plasma concentrations and monitoring of serum transaminases should be performed.</description><identifier>ISSN: 0140-7783</identifier><identifier>EISSN: 1365-2885</identifier><identifier>DOI: 10.1111/jvp.12994</identifier><identifier>PMID: 34165194</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Antifungal Agents - therapeutic use ; Camelids, New World ; coccidioidomycosis ; Fluconazole ; New World camelids ; pharmacokinetics</subject><ispartof>Journal of veterinary pharmacology and therapeutics, 2022-01, Vol.45 (1), p.99-106</ispartof><rights>2021 John Wiley & Sons Ltd</rights><rights>2021 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2854-7beb3b4a406da7758e159e6316a1b0fc33f1bbd67982a1a34639b131bfd9a2243</cites><orcidid>0000-0001-5019-7567</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjvp.12994$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjvp.12994$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27926,27927,45576,45577</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34165194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Butkiewicz, Christine D.</creatorcontrib><creatorcontrib>Shubitz, Lisa F.</creatorcontrib><creatorcontrib>Nix, David E.</creatorcontrib><title>A preliminary study of the plasma concentrations of orally administered fluconazole in alpacas (Vicugna pacos)</title><title>Journal of veterinary pharmacology and therapeutics</title><addtitle>J Vet Pharmacol Ther</addtitle><description>Alpacas residing in the region endemic for Coccidioides spp. are susceptible to serious, disseminated coccidioidomycosis that may result in death. There is currently no oral antifungal dose recommendation for this species. We used a steady‐state study design to assess the pharmacokinetics of oral generic fluconazole in alpacas dosed q 24 h for 14 days. Cohorts of 2–3 animals received fluconazole from 6 to 15 mg/kg/day, and pharmacokinetic analysis was performed after each group of animals in order to make dose adjustments for the next group. The final three animals were used as confirmation of our dose recommendation. The median Tmax was 7 h, and the median Cmax was 1.25 µg/ml per mg/kg dose. The mean dose‐normalized 24‐h AUC was 41.7 µg h/ml per mg/kg dose (CV = 72%). Based on these results, we recommend alpacas receive a starting dose of oral fluconazole at 10–15 mg/kg/day based on the fluconazole AUC in humans (313–625 µg h/ml). Testing to ascertain putative therapeutic plasma concentrations and monitoring of serum transaminases should be performed.</description><subject>Animals</subject><subject>Antifungal Agents - therapeutic use</subject><subject>Camelids, New World</subject><subject>coccidioidomycosis</subject><subject>Fluconazole</subject><subject>New World camelids</subject><subject>pharmacokinetics</subject><issn>0140-7783</issn><issn>1365-2885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1PwzAMhiMEYmNw4A-gHNmhW9ykX8cJ8alJcIBdK6dNIVPWVkkLKr-ejAI3fLEsP34lP4ScA1uAr-X2vV1AmGXigEyBx1EQpml0SKYMBAuSJOUTcuLcljHGU4BjMuEC4ggyMSX1irZWGb3TNdqBuq4vB9pUtHtTtDXodkiLpi5U3VnsdFO7_bKxaMxAsfRX2nXKqpJWpvcgfjZGUV1TNC0W6OjlRhf9a43Uj42bn5KjCo1TZz99Rl5urp-v7oL14-391WodFGEaiSCRSnIpULC4xCSJUgVRpmIOMYJkVcF5BVKWcZKlIQJyEfNMAgdZlRmGoeAzMh9zC9s4Z1WVt1bv_Ic5sHzvLPfO8m9nnr0Y2baXO1X-kb-SPLAcgQ9t1PB_Uv6weRojvwDc9nfU</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Butkiewicz, Christine D.</creator><creator>Shubitz, Lisa F.</creator><creator>Nix, David E.</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-5019-7567</orcidid></search><sort><creationdate>202201</creationdate><title>A preliminary study of the plasma concentrations of orally administered fluconazole in alpacas (Vicugna pacos)</title><author>Butkiewicz, Christine D. ; Shubitz, Lisa F. ; Nix, David E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2854-7beb3b4a406da7758e159e6316a1b0fc33f1bbd67982a1a34639b131bfd9a2243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Antifungal Agents - therapeutic use</topic><topic>Camelids, New World</topic><topic>coccidioidomycosis</topic><topic>Fluconazole</topic><topic>New World camelids</topic><topic>pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Butkiewicz, Christine D.</creatorcontrib><creatorcontrib>Shubitz, Lisa F.</creatorcontrib><creatorcontrib>Nix, David E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of veterinary pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Butkiewicz, Christine D.</au><au>Shubitz, Lisa F.</au><au>Nix, David E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A preliminary study of the plasma concentrations of orally administered fluconazole in alpacas (Vicugna pacos)</atitle><jtitle>Journal of veterinary pharmacology and therapeutics</jtitle><addtitle>J Vet Pharmacol Ther</addtitle><date>2022-01</date><risdate>2022</risdate><volume>45</volume><issue>1</issue><spage>99</spage><epage>106</epage><pages>99-106</pages><issn>0140-7783</issn><eissn>1365-2885</eissn><abstract>Alpacas residing in the region endemic for Coccidioides spp. are susceptible to serious, disseminated coccidioidomycosis that may result in death. There is currently no oral antifungal dose recommendation for this species. We used a steady‐state study design to assess the pharmacokinetics of oral generic fluconazole in alpacas dosed q 24 h for 14 days. Cohorts of 2–3 animals received fluconazole from 6 to 15 mg/kg/day, and pharmacokinetic analysis was performed after each group of animals in order to make dose adjustments for the next group. The final three animals were used as confirmation of our dose recommendation. The median Tmax was 7 h, and the median Cmax was 1.25 µg/ml per mg/kg dose. The mean dose‐normalized 24‐h AUC was 41.7 µg h/ml per mg/kg dose (CV = 72%). Based on these results, we recommend alpacas receive a starting dose of oral fluconazole at 10–15 mg/kg/day based on the fluconazole AUC in humans (313–625 µg h/ml). Testing to ascertain putative therapeutic plasma concentrations and monitoring of serum transaminases should be performed.</abstract><cop>England</cop><pmid>34165194</pmid><doi>10.1111/jvp.12994</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-5019-7567</orcidid></addata></record> |
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subjects | Animals Antifungal Agents - therapeutic use Camelids, New World coccidioidomycosis Fluconazole New World camelids pharmacokinetics |
title | A preliminary study of the plasma concentrations of orally administered fluconazole in alpacas (Vicugna pacos) |
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