560 AJVR • Vol 82 • No. 7 • July 2021 L imited information is available regarding anti- microbial administration and related pharma- cokinetic properties in amphibians. Consequently, current antimicrobial dosing strategies are based pri- marily on cross-species extrapolations from reptiles or mammals. Most of the published amphibian anti- microbial data pertain to a single study, 1 which dem- onstrated that skin bacterial loads decreased over time when Northern leopard frogs (Lithobates pipi- ens) were immersed in baths of various antimicrobial Pharmacokinetics of ceftazidime in Northern leopard frogs ( Lithobates pipiens) at two different doses and administration routes Shawna J. Hawkins MS, DVM Sherry K. Cox PhD Kurt K. Sladky MS, DVM Received September 7, 2020. Accepted November 23, 2020. From the Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madi- son, WI 53706 (Hawkins, Sladky); and Department of Comparative Medicine, College of Veterinary Medi- cine, University of Tennessee, Knoxville, TN 37996 (Cox). Address correspondence to Dr. Hawkins (shawkins0902@gmail.com). OBJECTIVE To determine an optimal ceftazidime dosing strategy in Northern leopard frogs ( Lithobates pipiens) by evaluation of 2 different doses administered SC and 1 dose administered transcutaneously. ANIMALS 44 Northern leopard frogs (including 10 that were replaced). PROCEDURES Ceftazidime was administered to frogs SC in a forelimb at 20 mg/kg (n = 10; SC20 group) and 40 mg/kg (10; SC40 group) or transcutaneously on the cranial dorsum at 20 mg/kg (10; TC20 group). Two frogs in each ceftazidime group were euthanized 12, 24, 48, 72, and 96 hours after drug administra- tion. Plasma, renal, and skin concentrations of ceftazidime were measured by means of reversed-phase high-performance liquid chromatography. Four control frogs were used for assay validation. RESULTS Mean plasma half-life of ceftazidime in the SC20, SC40, and TC20 groups was 9.01 hours, 14.49 hours, and too low to determine, respectively. Mean maximum plasma ceftazidime concentration was 92.9, 96.0, and 1.3 μg/mL, respectively. For 24 hours after drug administration in the SC20 and SC40 groups, plasma ceftazidime concentration exceeded 8 μg/mL. Renal and skin concentrations were detectable at both doses and routes of adminis- tration; however, skin concentrations were signifcantly lower than renal and plasma concentrations. CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that ceftazidime administration to Northern leopard frogs at 20 mg/kg, SC, every 24 hours would achieve a plasma concentration exceeding the value considered effective against common amphibian pathogens. Transcu- taneous administration of the injectable ceftazidime formulation at 20 mg/kg warrants further investigation but is not currently recommended because of a potential lack of effcacy. (Am J Vet Res 2021;82:560–565) solutions. Route of administration is an important fac- tor to consider because amphibian skin is highly per- meable, allowing for most chemicals to be absorbed systemically when applied topically. 2–4 This unique adaptation has led to the exploration of medications applied topically or via immersion, but few pharma- cokinetic studies have been performed to demon- strate that medications applied topically will reach effective plasma concentrations in amphibians. 3 Ceftazidime is a third generation cephalosporin that has broad-spectrum coverage and a particular af- finity for gram-negative bacteria, including Pseudo- monas spp. 5 Ceftazidime has a wide range of tissue dispersion in mammals (including bone and CSF) and is exclusively excreted, unchanged, by the kidneys. 5 The method of action is time dependent, and efficacy is defined by the time the serum or plasma concentra- tion remains above the MIC for a specific pathogen. 6 Although ceftazidime is a commonly used antimicro- bial in reptiles and is widely used in amphibians, few ABBREVIATIONS AUC Area under the concentration-versus-time curve AUC 0–∞ Area under the concentration-versus-time curve from time 0 to infnity C max Maximum plasma concentration HPLC High-performance liquid chromatography MIC Minimum inhibitory concentration t 1/2 Half-life TC Transcutaneous t max Time to maximum plasma concentration Unauthenticated | Downloaded 03/01/23 08:13 AM UTC