PMID- 35024493 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220115 IS - 2451-943X (Electronic) IS - 2451-943X (Linking) VI - 15 DP - 2022 Mar TI - Pharmacokinetics and analytical determination of acyclovir in Asian elephant calves (Elephas maximus). PG - 100227 LID - 10.1016/j.vas.2021.100227 [doi] LID - 100227 AB - A therapeutic regimen that includes antiviral drugs is critical for the survival of Asian elephant (Elephas maximus) calves infected with elephant endotheliotropic herpesvirus hemorrhagic disease (EEHV-HD), with acyclovir showing considerable promise. The purpose of this study was to determine the pharmacokinetics and bioavailability of acyclovir following intravenous (IV) and oral (PO) administration in Asian elephants. A single dose of acyclovir (15 mg/kg, IV or 45 mg/kg, PO) was administered to four healthy elephant calves, with a minimum 2-week washout period between treatments. Serial plasma samples were collected after each injection for acyclovir analysis using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. Maximum plasma acyclovir concentrations were 27.02 +/- 6.79 microg/mL at 0.94 +/- 0.31 h after IV administration, and 1.45 +/- 0.20 microg/mL at 3.00 +/- 0.70 h after PO administration. The half-life of the elimination phase (T(1/2)) was 5.84 +/- 0.74 and 8.74 +/- 2.47 h after IV and PO administration, respectively. After IV administration, acyclovir concentrations were higher than the half-maximal inhibitory concentration (IC(50)) of those found for herpes simplex virus (HSV) 1 and 2 in humans, and equid alpha herpesvirus-1 (EHV-1) for at least 12 h. By contrast, the bioavailability of oral administration was low, only 6.03 +/- 0.87%, so higher doses by that route likely are needed to be effective. Due to the high concentration of plasma acyclovir after IV administration, the dose may need to be adjusted to prevent any negative side effects. CI - (c) 2021 The Author(s). FAU - Khammesri, Siripat AU - Khammesri S AD - Center of Elephant and Wildlife Health and Research, Faculty of Veterinary Medicine, Chiang Mai University, Thailand. AD - Graduate Program in Veterinary Science, Faculty of Veterinary Medicine, Chiang Mai University, Thailand. FAU - Ampasavate, Chadarat AU - Ampasavate C AD - Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University Thailand. FAU - Hongwiset, Darunee AU - Hongwiset D AD - Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University Thailand. AD - Pharmacy Service Center, Faculty of Pharmacy, Chiang Mai University, Thailand. FAU - Mektrirat, Raktham AU - Mektrirat R AD - Department of Veterinary Biosciences and Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Thailand. FAU - Sangsrijan, Siriluk AU - Sangsrijan S AD - Pharmacy Service Center, Faculty of Pharmacy, Chiang Mai University, Thailand. FAU - Brown, Janine L AU - Brown JL AD - Center of Elephant and Wildlife Health and Research, Faculty of Veterinary Medicine, Chiang Mai University, Thailand. AD - Center for Species Survival, Smithsonian Conservation Biology Institute, Front Royal, VA, USA. FAU - Thitaram, Chatchote AU - Thitaram C AD - Center of Elephant and Wildlife Health and Research, Faculty of Veterinary Medicine, Chiang Mai University, Thailand. AD - Department of Companion Animal and Wildlife Clinic, Faculty of Veterinary Medicine, Chiang Mai University, Thailand. LA - eng PT - Journal Article DEP - 20211224 PL - Netherlands TA - Vet Anim Sci JT - Veterinary and animal science JID - 101694897 PMC - PMC8724961 OTO - NOTNLM OT - %CV, Mean precision OT - AUC0-inf, Total area under the plasma concentration-time curve from time zero to infinity OT - AUC0-t, Total area under the plasma concentration-time curve from time 0-48h OT - Acyclovir OT - Asian elephant OT - Bioavailability OT - Cl, Total clearance OT - Cmax, Peak plasma concentration OT - EEHV, Elephantendotheliotropic herpesviruses OT - EEHV-HD, Elephant endotheliotropic herpesvirus hemorrhagic disease OT - EHV, Equid alphaherpesvirus OT - Elephant endotheliotropic herpesvirus (EEHV) OT - F, Bioavailability OT - HSV, Herpes simplex virus OT - IV, Intravenous administration OT - Kel, Elimination rate constant OT - LC-MS/MS, Liquid chromatography-tandem mass spectrometry OT - LLOQ, Lower limit of quantitation OT - MAT, Mean absorption time OT - MRM, Multiple reaction monitoring OT - MRT, Mean residence time OT - PO, Oral administration OT - Pharmacokinetics OT - QC, Quality control OT - S/N, Signal to noise ratio OT - T1/2, Elimination half-life OT - Tmax, Time to reach peak plasma OT - Vd(ss), Steady-state volume of distribution OT - m/z, Mass-to-charge ratio OT - r2, Coefficients of determination COIS- None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper. EDAT- 2022/01/14 06:00 MHDA- 2022/01/14 06:01 PMCR- 2021/12/24 CRDT- 2022/01/13 12:34 PHST- 2021/10/04 00:00 [received] PHST- 2021/12/09 00:00 [revised] PHST- 2021/12/22 00:00 [accepted] PHST- 2022/01/13 12:34 [entrez] PHST- 2022/01/14 06:00 [pubmed] PHST- 2022/01/14 06:01 [medline] PHST- 2021/12/24 00:00 [pmc-release] AID - S2451-943X(21)00062-4 [pii] AID - 100227 [pii] AID - 10.1016/j.vas.2021.100227 [doi] PST - epublish SO - Vet Anim Sci. 2021 Dec 24;15:100227. doi: 10.1016/j.vas.2021.100227. eCollection 2022 Mar.