{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:40:07Z","timestamp":1774690807761,"version":"3.50.1"},"reference-count":32,"publisher":"American Veterinary Medical Association (AVMA)","issue":"7","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants (<jats:italic>Loxodonta africana<\/jats:italic>).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>ANIMALS<\/jats:title>\n<jats:p>15 African elephants (6 males and 9 females) of various ages.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>METHODS<\/jats:title>\n<jats:p>Famciclovir (15 mg\/kg) was administered orally or per rectum once, with at least a three-week washout period between administrations. Blood was collected at 13 different timepoints per administration for 6 elephants, occurring between February and March 2020. An additional 9 elephants were sampled at variable timepoints per administration utilizing a sparse sampling design between July 2020 and January 2021. Plasma famciclovir and penciclovir levels were measured via HPLC and fluorescence detection. Pharmacokinetic analysis was completed in the summer of 2021 using noncompartmental analysis and nonlinear mixed-effects modeling.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>RESULTS<\/jats:title>\n<jats:p>Famciclovir was not detected in any sample, suggesting complete metabolism. Key pharmacokinetic parameters for penciclovir following oral administration were time to maximum concentration (t<jats:sub>max<\/jats:sub>; 2.12 hours), area under the concentration-versus-time curve (AUC; 33.93 \u03bcg\u00b7h\/mL), maximum observed concentration (C<jats:sub>max<\/jats:sub>; 3.73 \u03bcg\/mL), and absorption half-life (t<jats:sub>1\/2<\/jats:sub>; 0.65 hours). Following rectal administration, the values were: t<jats:sub>max<\/jats:sub>, 0.65 hours; AUC, 15.62 \u03bcg\u00b7h\/mL; C<jats:sub>max<\/jats:sub>, 2.52 \u03bcg\/mL; and absorption t<jats:sub>1\/2<\/jats:sub>, 0.13 hours.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>Famciclovir was rapidly metabolized to penciclovir. Oral administration resulted in slower absorption but higher maximum plasma concentration and higher AUC compared to rectal administration.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a6\">\n<jats:title>CLINICAL RELEVANCE<\/jats:title>\n<jats:p>African elephants administered famciclovir via oral and rectal routes resulted in measurable serum penciclovir, and these findings may be utilized by clinicians treating viral infections in this species.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.24.02.0039","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T19:40:46Z","timestamp":1714419646000},"source":"Crossref","is-referenced-by-count":1,"title":["Penciclovir pharmacokinetics after oral and rectal administration of famciclovir in African elephants (Loxodonta africana) shows that effective concentrations can be achieved from rectal administration, despite lower absorption"],"prefix":"10.2460","volume":"85","author":[{"given":"John A.","family":"Griffioen","sequence":"first","affiliation":[{"name":"Fort Worth Zoo, Fort Worth, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa A.","family":"Fayette","sequence":"additional","affiliation":[{"name":"Indianapolis Zoo, Indianapolis, IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffry S.","family":"Proudfoot","sequence":"additional","affiliation":[{"name":"Indianapolis Zoo, Indianapolis, IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren L.","family":"Howard","sequence":"additional","affiliation":[{"name":"San Diego Zoo Safari Park, Escondido, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark G.","family":"Papich","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"issue":"3","key":"B1","series-title":"ILAR J","first-page":"283","article-title":"Review of elephant endotheliotropic herpesvirus and acute hemorrhagic disease","volume":"56","author":"Long SY","year":"2015","unstructured":"Long SY, Latimer EM, Hayward GS. Review of elephant endotheliotropic herpesvirus and acute hemorrhagic disease. ILAR J. 2015;56(3):283\u2013296. doi:10.1093\/ilar\/ilv041"},{"issue":"2","key":"B2","series-title":"J Zoo Wildl Med","first-page":"335","article-title":"Epidemiologic evaluation of elephant endotheliotropic herpesvirus 3B infection in an African elephant (Loxodonta africana)","volume":"48","author":"Bronson E","year":"2017","unstructured":"Bronson E, McClure M, Sohl J, et al. Epidemiologic evaluation of elephant endotheliotropic herpesvirus 3B infection in an African elephant (Loxodonta africana). J Zoo Wildl Med. 2017;48(2):335\u2013343. doi:10.1638\/2016-0063R.1"},{"issue":"1","key":"B3","series-title":"J Zoo Wildl Med","first-page":"357","article-title":"Acute hemorrhagic disease due to elephant endotheliotropic herpesvirus 3A infection in five African elephants (Loxodonta africana) at one North American zoological institution","volume":"52","author":"Fayette MA","year":"2021","unstructured":"Fayette MA, Brenner EE, Garner MM, Bowman MR, Latimer E, Proudfoot JS. Acute hemorrhagic disease due to elephant endotheliotropic herpesvirus 3A infection in five African elephants (Loxodonta africana) at one North American zoological institution. J Zoo Wildl Med. 2021;52(1):357\u2013365. doi:10.1638\/2020-0126"},{"issue":"5405","key":"B4","series-title":"Science","first-page":"1171","article-title":"Novel endotheliotropic herpesvirus fatal for Asian and African elephants","volume":"283","author":"Richman LK","year":"1999","unstructured":"Richman LK, Montali RJ, Garer RI, et al. Novel endotheliotropic herpesvirus fatal for Asian and African elephants. Science. 1999;283(5405):1171\u20131176. doi:10.1126\/science.283.5405.1171"},{"issue":"1","key":"B5","series-title":"J Wildl Dis","first-page":"1","article-title":"Clinical and pathological findings of a newly recognized disease of elephants caused by endotheliotropic herpesviruses","volume":"36","author":"Richman LK","year":"2000","unstructured":"Richman LK, Montali RJ, Cambre RC, et al. Clinical and pathological findings of a newly recognized disease of elephants caused by endotheliotropic herpesviruses. J Wildl Dis. 2000;36(1):1\u201312. doi:10.7589\/0090-3558-36.1.1"},{"issue":"1","key":"B6","series-title":"J Zoo Wildl Med","first-page":"311","article-title":"Clinical infection of captive Asian elephants (Elephas maximus) with elephant endotheliotropic herpesvirus 4","volume":"47","author":"Fuery A","year":"2016","unstructured":"Fuery A, Browning GR, Tan J, et al. Clinical infection of captive Asian elephants (Elephas maximus) with elephant endotheliotropic herpesvirus 4. J Zoo Wildl Med. 2016;47(1):311\u2013318. doi:10.1638\/2015-0072.1"},{"issue":"1","key":"B7","series-title":"J Zoo Wildl Med","first-page":"319","article-title":"Clinical infection of two captive Asian elephants (Elephas maximus) with elephant endotheliotropic herpesvirus 1B","volume":"47","author":"Fuery A","year":"2016","unstructured":"Fuery A, Tan J, Peng R, et al. Clinical infection of two captive Asian elephants (Elephas maximus) with elephant endotheliotropic herpesvirus 1B. J Zoo Wildl Med. 2016;47(1):319\u2013324. doi:10.1638\/2015-0074.1"},{"issue":"1-2","key":"B8","series-title":"Vet Microbiol","first-page":"28","article-title":"Detection and evaluation of novel herpesviruses in routine and pathological samples from Asian and African elephants: identification of two new probosciviruses (EEHV5 and EEHV6) and two new gammaherpesviruses (EGHV3B and EGHV5)","volume":"147","author":"Latimer E","year":"2011","unstructured":"Latimer E, Zong JC, Heaggans SY, Richman L, Hayward GS. Detection and evaluation of novel herpesviruses in routine and pathological samples from Asian and African elephants: identification of two new probosciviruses (EEHV5 and EEHV6) and two new gammaherpesviruses (EGHV3B and EGHV5). Vet Microbiol. 2011;147(1-2):28\u201341. doi:10.1016\/j.vetmic.2010.05.042"},{"key":"B9","first-page":"41","author":"Kongmakee P","year":"2015","unstructured":"Kongmakee P, Suttiyaporn S, Changpetch W, et al. Elephant endotheliotropic herpesvirus type 6 infection in a captive African elephant (Loxodonta africana) in Thailand. In: Proceedings from the EEHV 2015 Workshop on Elephant Endotheliotropic Herpesvirus; 2015:41."},{"issue":"23","key":"B10","series-title":"J Virol","first-page":"13523","article-title":"Elephant endotheliotropic herpesviruses EEHV1A, EEHV1B, and EEHV2 from cases of hemorrhagic disease are highly diverged from other mammalian herpesviruses and may form a new subfamily","volume":"88","author":"Richman LK","year":"2014","unstructured":"Richman LK, Zong JC, Latimer EM, et al. Elephant endotheliotropic herpesviruses EEHV1A, EEHV1B, and EEHV2 from cases of hemorrhagic disease are highly diverged from other mammalian herpesviruses and may form a new subfamily. J Virol. 2014;88(23):13523\u201313546. doi:10.1128\/JVI.01673-14"},{"issue":"1","key":"B11","series-title":"J Zoo Wildl Med","first-page":"136","article-title":"Elephant endotheliotropic herpesvirus 5, a newly recognized elephant herpesvirus associated with clinical and subclinical infections in captive Asian elephants (Elephas maximus)","volume":"44","author":"Atkins L","year":"2013","unstructured":"Atkins L, Zong JC, Tan J, et al. Elephant endotheliotropic herpesvirus 5, a newly recognized elephant herpesvirus associated with clinical and subclinical infections in captive Asian elephants (Elephas maximus). J Zoo Wildl Med. 2013;44(1):136\u2013143. doi:10.1638\/1042-7260-44.1.136"},{"issue":"1","key":"B12","series-title":"BMC Vet Res","first-page":"178","article-title":"Surviving and fatal elephant endotheliotropic herpesvirus-1A infections in juvenile Asian elephants \u2013 lessons learned and recommendations on anti-herpesviral therapy","volume":"12","author":"Dastjerdi A","year":"2016","unstructured":"Dastjerdi A, Seilern-Moy K, Darpel K, Steinbach F, Molenaar F. Surviving and fatal elephant endotheliotropic herpesvirus-1A infections in juvenile Asian elephants \u2013 lessons learned and recommendations on anti-herpesviral therapy. BMC Vet Res. 2016;12(1):178\u2013188. doi:10.1186\/s12917-016-0806-5"},{"issue":"4","key":"B13","series-title":"J Zoo Wildl Med","first-page":"518","article-title":"Use of famciclovir for the treatment of endotheliotropic herpesvirus infections in Asian elephants (Elephas maximus)","volume":"31","author":"Schmitt DL","year":"2000","unstructured":"Schmitt DL, Hardy DA, Montali RJ, et al. Use of famciclovir for the treatment of endotheliotropic herpesvirus infections in Asian elephants (Elephas maximus). J Zoo Wildl Med. 2000;31(4):518\u2013522."},{"issue":"12","key":"B14","series-title":"Am J Vet Res","first-page":"1996","article-title":"Estimates of the pharmacokinetics of famciclovir and its active metabolite penciclovir in young Asian elephants (Elephas maximus)","volume":"73","author":"Brock AP","year":"2012","unstructured":"Brock AP, Isaza R, Hunter RP, et al. Estimates of the pharmacokinetics of famciclovir and its active metabolite penciclovir in young Asian elephants (Elephas maximus). Am J Vet Res. 2012;73(12):1996\u20132000. doi:10.2460\/ajvr.73.12.1996"},{"issue":"4","key":"B15","series-title":"J Zoo Wildl Med","first-page":"670","article-title":"Pharmacokinetics of rectally and orally administered levofloxacin in Asian elephants (Elephas maximus)","volume":"53","author":"Kilburn JJ","year":"2023","unstructured":"Kilburn JJ, Schmitt D, Kiso W, Papich MG, Backues KA. Pharmacokinetics of rectally and orally administered levofloxacin in Asian elephants (Elephas maximus). J Zoo Wildl Med. 2023;53(4):670\u2013678. doi:10.1638\/2022-0011"},{"issue":"1","key":"B16","series-title":"J Zoo Wildl Med","first-page":"1","article-title":"Pharmacokinetics of a single dose of metronidazole after rectal administration in captive Asian elephants (Elephas maximus)","volume":"47","author":"Sander SJ","year":"2016","unstructured":"Sander SJ, Siegal-Willot JL, Ziegler J, Lee E, Tell L, Murray S. Pharmacokinetics of a single dose of metronidazole after rectal administration in captive Asian elephants (Elephas maximus). J Zoo Wildl Med. 2016;47(1):1\u20135. doi:10.1638\/2015-0160.1"},{"issue":"2","key":"B17","series-title":"Antiviral Chem Chemother","first-page":"67","article-title":"Famciclovir and penciclovir. The mode of action of famciclovir including its conversion to penciclovir","volume":"4","author":"Vere Hodge RA","year":"1993","unstructured":"Vere Hodge RA. Famciclovir and penciclovir. The mode of action of famciclovir including its conversion to penciclovir. Antiviral Chem Chemother. 1993;4(2):67\u201384. doi:10.1177\/095632029300400201"},{"issue":"2","key":"B18","series-title":"J Zoo Wildl Med","first-page":"258","article-title":"Pharmacokinetics of orally administered ibuprofen in African and Asian elephants (Loxodonta africana and Elephas maximus)","volume":"38","author":"Bechert U","year":"2007","unstructured":"Bechert U, Christensen JM. Pharmacokinetics of orally administered ibuprofen in African and Asian elephants (Loxodonta africana and Elephas maximus). J Zoo Wildl Med. 2007;38(2):258\u2013268. doi:10.1638\/1042-7260(2007)038[0258:POOAII"},{"issue":"2","key":"B19","series-title":"J Zoo Wildl Med","first-page":"188","article-title":"Pharmacokinetics of orally administered phenylbutazone in African and Asian elephants (Loxodonta africana and Elephas maximus)","volume":"39","author":"Bechert U","year":"2008","unstructured":"Bechert U, Christensen JM, Nguyen C, Neelkant R, Bendas E. Pharmacokinetics of orally administered phenylbutazone in African and Asian elephants (Loxodonta africana and Elephas maximus). J Zoo Wildl Med. 2008;39(2):188\u2013200. doi:10.1638\/2007-0139R.1"},{"issue":"4","key":"B20","series-title":"J Zoo Wildl Med","first-page":"905","article-title":"Pharmacokinetics of orally administered flunixin meglumine in African (Loxodonta africana) and Asian (Elephas maximus) elephants","volume":"51","author":"Bechert U","year":"2021","unstructured":"Bechert U, Christensen JM, Kottwitz J, Boothe D, Alshahrani S, Mohammed S. Pharmacokinetics of orally administered flunixin meglumine in African (Loxodonta africana) and Asian (Elephas maximus) elephants. J Zoo Wildl Med. 2021;51(4):905\u2013914. doi:10.1638\/2020-0053"},{"issue":"4","key":"B21","series-title":"J Zoo Wildl Med","first-page":"409","article-title":"Comparative pharmacokinetics of trimethoprim-sulfamethoxazole administered intravenously and orally to captive elephants","volume":"22","author":"Page CD","year":"1991","unstructured":"Page CD, Mautino M, Derendorf HD, Anhalt JP. Comparative pharmacokinetics of trimethoprim-sulfamethoxazole administered intravenously and orally to captive elephants. J Zoo Wildl Med. 1991;22(4):409\u2013416."},{"key":"B22","series-title":"Eur J Wild Res","first-page":"68","article-title":"Observations on the length of the intestinal tract of African Loxodonta africana (Blumenbach 1797) and Asian elephants Elephas maximus (Linne 173)","volume":"53","author":"Clauss M","year":"2007","unstructured":"Clauss M, Steinmetz H, Eulenberger U, et al. Observations on the length of the intestinal tract of African Loxodonta africana (Blumenbach 1797) and Asian elephants Elephas maximus (Linne 173). Eur J Wild Res. 2007;53:68\u201372. doi:10.1007\/s10344-006-0064-0"},{"issue":"1","key":"B23","series-title":"J Zoo Aquar Res","first-page":"1","article-title":"A review of Asian and African elephant gastrointestinal anatomy, physiology, and pharmacology: elephant gastrointestinal anatomy, physiology, and pharmacology","volume":"7","author":"Greene W","year":"2019","unstructured":"Greene W, Dierenfeld ES, Mikota S. A review of Asian and African elephant gastrointestinal anatomy, physiology, and pharmacology: elephant gastrointestinal anatomy, physiology, and pharmacology. J Zoo Aquar Res. 2019;7(1):1\u201314."},{"key":"B24","series-title":"Comparative Physiology of the Vertebrate Digestive System","author":"Stevens CS","year":"1995","unstructured":"Stevens CS, Hume ID. Comparative Physiology of the Vertebrate Digestive System. 2nd ed. Cambridge University Press; 1995."},{"key":"B25","unstructured":"Accreditation Standards & Related Policies. Association of Zoos and Aquariums. Accessed January 1, 2024. https:\/\/assets.speakcdn.com\/assets\/2332\/aza-accreditation-standards.pdf"},{"key":"B26","unstructured":"Validation of Analytical Procedures: Text and Methodology. International Conference on Harmonisation of Technical Requirements for Requirements for Registration of Pharmaceuticals for Human Use. Updated November, 2005. Accessed September 1, 2021. https:\/\/database.ich.org\/sites\/default\/files\/Q2%28R1%29%20Guideline.pdf"},{"key":"B27","series-title":"General Chapter, (1225) Validation of Compendial Procedures","year":"2021","unstructured":"United States Pharmacopeia. General Chapter, (1225) Validation of Compendial Procedures. USP-NF. United States Pharmacopeia; 2021. doi:10.31003\/USPNF_M99945_04_01"},{"issue":"1\u20132","key":"B28","series-title":"J Virol Methods","first-page":"85","article-title":"Development of a quantitative real-time TaqMan PCR assay for testing the susceptibility of feline herpesvirus-1 to antiviral compounds","volume":"152","author":"Hussein IT","year":"2008","unstructured":"Hussein IT, Field HJ. Development of a quantitative real-time TaqMan PCR assay for testing the susceptibility of feline herpesvirus-1 to antiviral compounds. J Virol Methods. 2008;152(1\u20132):85\u201390. doi:10.1016\/j.jviromet.2008.05.018"},{"issue":"3","key":"B29","series-title":"Antiviral Res","first-page":"268","article-title":"Penciclovir is a potent inhibitor of feline herpesvirus-1 with susceptibility determined at the level of virus-encoded thymidine kinase","volume":"78","author":"Hussein IT","year":"2008","unstructured":"Hussein IT, Menashy RV, Field HJ. Penciclovir is a potent inhibitor of feline herpesvirus-1 with susceptibility determined at the level of virus-encoded thymidine kinase. Antiviral Res. 2008;78(3):268\u2013274. doi:10.1016\/j.antiviral.2007.10.015"},{"key":"B30","series-title":"Curr Eye Res","first-page":"215","article-title":"Efficacy of antiviral agents in feline herpetic keratitis: results of an in vitro study","volume":"2-3)","author":"Williams DL","year":"2004","unstructured":"Williams DL, Fitzmaurice T, Lay L, et al. Efficacy of antiviral agents in feline herpetic keratitis: results of an in vitro study. Curr Eye Res. 2004;(2-3):215\u2013218. doi:10.1080\/02713680490504849"},{"key":"B31","series-title":"Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases","first-page":"577","article-title":"Antivirals against herpesviruses","author":"Aoki FY","year":"2020","unstructured":"Aoki FY. Antivirals against herpesviruses. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Elsevier; 2020:577\u2013595."},{"issue":"1","key":"B32","series-title":"Antiviral Res","first-page":"77","article-title":"The acyclic nucleoside analogue penciclovir is a potent inhibitor of equine herpesvirus type 1 (EHV-1) in tissue culture and in a murine model","volume":"18","author":"de la Fuente R","year":"1992","unstructured":"de la Fuente R, Awan AR, Field HJ. The acyclic nucleoside analogue penciclovir is a potent inhibitor of equine herpesvirus type 1 (EHV-1) in tissue culture and in a murine model. Antiviral Res. 1992;18(1):77\u201389. doi:10.1016\/0166-3542(92)90007-R"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/85\/7\/ajvr.24.02.0039.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/85\/7\/ajvr.24.02.0039.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/85\/7\/ajvr.24.02.0039.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T17:27:16Z","timestamp":1727803636000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/85\/7\/ajvr.24.02.0039.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":32,"journal-issue":{"issue":"7"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.24.02.0039","relation":{},"ISSN":["0002-9645","1943-5681"],"issn-type":[{"value":"0002-9645","type":"print"},{"value":"1943-5681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,1]]}}}