Journal of veterinary pharmacology and therapeutics最新文献

{"title":"Preclinical Target Animal Safety Evaluation of Veterinary Monoclonal Antibodies: Principles, Methods, and Interpretation.","authors":"Adam Werts, Matthew Kuhn, Lauren Bessey, Alicia Braxton Hickman, Emily Chory, John Mitchell, Kirby Pasloske","doi":"10.1111/jvp.70116","DOIUrl":"https://doi.org/10.1111/jvp.70116","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) represent a rapidly expanding pharmaceutical class in veterinary medicine, with several products now authorized for use in dogs and cats. Limited published articles and veterinarian exposure to the principles of drug development present challenges in interpreting published safety evaluations that inform product labeling and clinical use. This review describes the principles, methods, strengths, limitations, and interpretation of preclinical target animal safety (TAS) studies for veterinary mAbs and is intended to equip veterinarians and researchers with the knowledge to critically evaluate published TAS data and understand how preclinical safety evidence translates to product labeling. TAS studies are conducted in healthy, purpose-bred animals of the target species using a margin of safety (MOS) approach with supratherapeutic dosing to screen for product risks. The regulatory and scientific framework is based on internationally harmonized guidance for safety evaluation of small molecule therapeutics in veterinary medicine and more than four decades of experience with mAb therapeutics in human medicine. The high target specificity of the mAb drug class enables a hypothesis-driven evaluation strategy, combining standard endpoints with target-informed specialized assessments. Terminal gross and histopathological endpoints provide safety data that clinical studies cannot generate, identifying potential adverse effects down to the cellular level. Unique to veterinary medicine, these data are generated directly in the target species. Data interpretation follows a weight-of-evidence approach in which findings are presumed treatment-related until demonstrated otherwise, integrating dose-response relationships, biological plausibility, and both study and historical control data. TAS studies complement the broader safety evaluation continuum, including clinical field studies, pharmacovigilance, and independent research.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue Depletion in Dairy Cattle Following Administration of Label or Extralabel Doses of Penicillin G Using Two Different Formulations.","authors":"Michael J Myers, O Alberto Chiesa, Linge Li, Karyn D Howard, Rachael Cohen, Raoul Gonzales","doi":"10.1111/jvp.70115","DOIUrl":"https://doi.org/10.1111/jvp.70115","url":null,"abstract":"<p><p>Penicillin G has been one of the main violative residues detected at slaughter for 25+ years. Accordingly, a residue depletion study was initiated to determine possible reasons, using a two-phase approach. Phase 1 involved a 2 × 2 matrix using either the 4- or 14-day withdrawal period product at label dosage (1×) or three times the label dose (3×), with tissues collected by laparoscopy. Phase 2 employed just a 3× dose of both products, with tissues collected at necropsy. Plasma and muscle penicillin G levels were below 50 ng/g (official tolerance level: 0.050 ppm) before the 4 and 14-day withdrawal period when dosed at 1× and 3×. Penicillin G in kidney and liver samples from heifers administered the 14-day withdrawal product were always below 50 ng/g by Day 14 regardless of dose or means of tissue collection. Kidney and liver concentration of Pen G from laparoscopically collected samples were in close agreement with results obtained from whole organ analyses. Administration of the 1× dose for the 4-day withdrawal period product resulted in residues in kidneys above 50 ng/g in 25% of study heifers (2 of 8) and in 50% (4 of 8) or more (3 of 5) following a 3× label dose.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Drug Knowledge to Therapeutic Competence: Active Learning for Competency-Based Veterinary Pharmacology Education.","authors":"Martin Hawes, Arno Werners","doi":"10.1111/jvp.70112","DOIUrl":"https://doi.org/10.1111/jvp.70112","url":null,"abstract":"","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Buccally Administered Cannabidiol and Oral Carprofen During Single- and Repeated-Dose Administration in Dogs.","authors":"Tilen Vake, Katerina Tomsič, Žiga Žgank, Mihaela Klasić, Janja Babič, Zlatka Bajc, Jožica Dolenc, Gabrijela Tavčar Kalcher, Odon Planinšek, Tomaž Snoj","doi":"10.1111/jvp.70114","DOIUrl":"https://doi.org/10.1111/jvp.70114","url":null,"abstract":"<p><p>Cannabidiol (CBD) is increasingly used as an adjunct treatment for chronic pain in dogs, but information on repeated-dose pharmacokinetics and potential interactions with commonly used analgesics remains limited. This study evaluated the pharmacokinetics of buccally administered CBD, its major metabolites, and orally administered carprofen in dogs, and assessed potential pharmacokinetic changes during co-administration. Twenty-five dogs with osteoarthritis received CBD (2 mg/kg), carprofen (2 mg/kg), or both drugs twice daily for 4 weeks. Plasma samples were collected during the first 12 h after the initial dose and at two and 4 weeks of treatment. Cannabidiol, 7-hydroxy-cannabidiol (7-OH-CBD), 7-carboxy-cannabidiol (7-COOH-CBD), and carprofen concentrations were quantified using LC-MS/MS. Pharmacokinetic parameters were estimated using non-compartmental and compartmental analyses. Cannabidiol was rapidly absorbed but showed substantial interindividual variability. CBD exposure was higher during co-administration with carprofen, but differences in C_max and AUC_last were not significant. Repeated dosing resulted in increasing 2-h post-dose CBD concentrations over time. Among metabolites, 7-COOH-CBD showed greater exposure and persistence than 7-OH-CBD. Carprofen pharmacokinetics were consistent with previous reports, with higher but non-significant C_max and AUC_last during co-administration with CBD. These findings warrant further investigation of potential pharmacokinetic interactions between CBD and carprofen.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering Transporter-Mediated Drug Interactions Affecting Marbofloxacin Residues in Sheep Milk: From In Silico Predictions to In Vivo Validation.","authors":"Konstantinos V Arsenopoulos, Evroula Hapeshis, Elias Papadopoulos, Manos C Vlasiou","doi":"10.1111/jvp.70113","DOIUrl":"https://doi.org/10.1111/jvp.70113","url":null,"abstract":"<p><p>Veterinary drug residues in milk represent an important food safety concern, particularly under conditions of co-administration where transporter-mediated drug-drug interactions may alter residue profiles. Marbofloxacin, a fluoroquinolone antimicrobial, is actively secreted into milk through the ATP-binding cassette transporter ABCG2 (BCRP), whereas ivermectin has been reported to interact with ABC transporters. The present study integrated in silico and in vivo approaches to investigate whether ivermectin may influence marbofloxacin secretion into sheep milk through transporter-mediated mechanisms. A homology model of ovine ABCG2 was constructed using the human cryo-electron microscopy structure as a template. Molecular docking and molecular dynamics simulations were subsequently performed to evaluate ligand-transporter interactions and complex stability. Docking analysis demonstrated that ivermectin exhibited a broader and more favorable interaction profile within the ABCG2 transmembrane cavity compared with marbofloxacin, with partial overlap at residues associated with substrate recognition, particularly within the Asp129-Asp130 region. Molecular dynamics simulations confirmed stable accommodation of ivermectin within the transporter throughout the simulation period without structural destabilization of the protein. The in vivo component included lactating dairy ewes receiving marbofloxacin alone or in combination with ivermectin under routine field conditions. Milk samples collected at the predicted peak milk concentration were analyzed using a validated HPLC-PDA/MS method. Marbofloxacin was detected in all milk samples with high analytical specificity. Ewes treated with ivermectin exhibited significantly lower marbofloxacin concentrations in milk compared with animals receiving marbofloxacin alone, while significant within-animal variability between udder halves was also observed.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ursodeoxycholic Acid Oral Pharmacokinetics and Plasma Bile Acid Profile Changes in a Population of Healthy Neonatal Foals.","authors":"T N Burdette, B Delvescovo, E Wise Bellin, T J Divers, C G Donnelly","doi":"10.1111/jvp.70111","DOIUrl":"https://doi.org/10.1111/jvp.70111","url":null,"abstract":"<p><p>Ursodeoxycholic acid (UDCA) is a secondary bile acid used in humans for the treatment of some cholestatic diseases. Interest in its potential use in equine patients with liver conditions has increased. Pharmacokinetic parameters in adult horses have recently been reported; however, they are not available for foals. The objective of this study was to characterize the pharmacokinetics of UDCA following a single oral dose of 15 mg/kg in six healthy neonatal foals and evaluate associated changes in bile acids (BA) profile. UDCA concentrations were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis demonstrated median peak concentration (C_max) of 23.74 μmol (range 12.86-38.02 μmol) obtained at 5.5 h (range 2-6 h) (T_max). Concentrations declined by 24 h post-dosing, with minimal levels detected between 48 and 72 h. The median half-life was calculated to be 10.32 h (range 8.05-19.12 h), and the estimated mean dosing interval was approximately 12 h. Following administration, plasma UDCA concentrations increased substantially, with marked shift in BA profiles resulting in an increase in the proportion of UDCA relative to other BAs. These results suggest that an oral UDCA dose of 15 mg/kg administered every 12 h is likely appropriate for neonatal foals.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary Comparison of Competitive Efflux and Historical Transwell Assays for Assessing Canine P-Glycoprotein Substrate Status of Eleven Drugs Representing Ten Different Drug Classes.","authors":"K L Mealey, N S Burke","doi":"10.1111/jvp.70110","DOIUrl":"https://doi.org/10.1111/jvp.70110","url":null,"abstract":"<p><p>Because P-glycoprotein (P-gp) influences the disposition of substrate drugs, regulatory agencies recommend ascertaining the P-gp substrate status of active pharmaceutical ingredients (API's) intended for humans. Transwell-based assays using P-gp-overexpressing human cell lines are routinely used to predict the API's P-gp substrate status. Although ABCB1-1Δ-mediated P-gp deficiency contributes to serious canine adverse drug reactions, assessment of canine P-gp status is not currently recommended by regulatory agencies for canine API's. We have previously employed a competitive efflux assay to assess drugs as canine P-gp substrates as it affords some advantages over transwell assays. Our objective was to preliminarily compare results generated from these two methods using historical data for transwell assays. Eleven drugs were assessed as canine P-gp substrates by both methods, with two identified as non-P-gp substrates (erythromycin, propranolol) and nine identified as canine P-gp substrates (clarithromycin, daunorubicin, digoxin, etoposide, paclitaxel, quinidine, ritonavir, verapamil, vinblastine). Erythromycin was identified as a canine P-gp substrate by competitive efflux assay at roughly 10-fold higher concentrations than was used for transwell assays. Concordance of these methods assessing canine P-gp substrate status using historical data supports the need for head-to-head studies comparing these two methods for identifying canine P-gp substrates.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Pharmacokinetics and Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses\".","authors":"","doi":"10.1111/jvp.70109","DOIUrl":"https://doi.org/10.1111/jvp.70109","url":null,"abstract":"","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Population Pharmacokinetic Model of Gentamicin in Hospitalized Neonatal Foals.","authors":"Astrid J van den Brom-Spierenburg, Esther A Winter, Mathijs J P Theelen, Ingeborg M van Geijlswijk, Cornélie M Westermann, Marianne M Sloet van Oldruitenborgh-Oosterbaan, Tim Florschütz, Johannes C Vendrig, Esther W Siegers, Kim de Graaf, Marc Cherlet, Mathias Devreese, Ronette Gehring","doi":"10.1111/jvp.70108","DOIUrl":"https://doi.org/10.1111/jvp.70108","url":null,"abstract":"<p><p>Information on safe and effective gentamicin dosing in foals is limited. This study aimed to provide guidance regarding optimal dosing regimens by means of a population pharmacokinetic (popPK) model. Gentamicin plasma concentration of 290 samples from 72 hospitalized foals (≤ 14 days old), treated with intravenous (IV) gentamicin, was measured using a validated LC-MS/MS method. A 2-compartment popPK model was developed with age as a significant covariate on clearance. The final popPK model was used to simulate the commonly used clinical dosing regimens. Mean simulated fAUC_0-24H (10th-90th percentile) in respectively 1-day-old and 14-day-old foals following IV administration of 6.6 mg/kg q24h was 66.3 mg/L*h (44.7-91.2) and 41.9 mg/L*h (26.0-61.0) and following 12 mg/kg q36h 120.5 mg/L*h (81.3-165.8) and 76.2 mg/L*h (47.3-110.9). Trough concentrations were < 2 mg/L for both dosing regimens, irrespective of age. Based on a pharmacodynamic target of fAUC_0-24H/MIC > 80, the 12 mg/kg q36h regimen has a higher probability of target attainment (PTA) than 6.6 mg/kg q24h. A simulated hypothetical dose of 15 mg/kg q36h demonstrated promising PTA with mean trough values ≤ 2 mg/L. Despite substantial interindividual variability, the model provides a rational basis for selecting a dosing regimen in hospitalized neonatal foals.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Pharmacodynamic Analysis of Trimethoprim-Sulfonamide Combination Activity Against Staphylococcus pseudintermedius.","authors":"Andrew Mead, Alexis Viel, Marine Boulanger, Gudrun Overesch, Carl Ekstrand, Pierre-Louis Toutain, Aude A Ferran, Ludovic Pelligand","doi":"10.1111/jvp.70107","DOIUrl":"https://doi.org/10.1111/jvp.70107","url":null,"abstract":"<p><p>Trimethoprim (TMP)-sulfonamide combinations are widely used in veterinary medicine, yet the quantitative nature of their pharmacodynamic interaction remains incompletely characterised. This study investigated the interaction between TMP and sulfamethoxazole (SMX), sulfadiazine (SDZ) and sulfadimethoxine (SDMX) against two Staphylococcus pseudintermedius isolates using minimum inhibitory concentration (MIC) testing, time-kill curve (TKC) experiments and semi-mechanistic pharmacodynamic modelling incorporating a General Pharmacodynamic Interaction (GPDI) framework. TKC assays demonstrated enhanced antibacterial activity for TMP-sulfonamide combinations compared with monotherapy, with the greatest bacterial killing observed at TMP:sulfonamide ratios of 1:4 and 1:19. The final GPDI model identified a predominantly unidirectional interaction in which sulfonamides increased TMP potency through concentration-dependent reductions in TMP EC₅₀ of 86%-96% at saturating sulfonamide concentrations, corresponding to approximately 7- to 26-fold maximal possible increases in TMP potency. Maximal synergy differed between sulfonamides, occurring at approximately 1:20 for TMP/SMX (~75% increase in killing), 1:40 for TMP/SDZ (~181%) and 1:5 for TMP/SDMX (~80%). Pharmacokinetic-pharmacodynamic simulations of clinically relevant canine dosing regimens predicted transient bacterial suppression but not bacterial eradication. These findings demonstrate that TMP-sulfonamide synergy is dynamic, concentration-dependent and bacterial species-specific, highlighting the importance of PK/PD-informed optimisation of potentiated sulfonamide therapy in veterinary medicine.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}