Journal of veterinary pharmacology and therapeutics最新文献

{"title":"A Randomized, Blinded, Placebo-Controlled Crossover Study of the Pharmacokinetics and Pharmacodynamics of Naloxone, Naltrexone, and Nalmefene in Methadone-Sedated Working Dogs","authors":"Travis Mills,&nbsp;Mary A. Robinson,&nbsp;Ciara Barr,&nbsp;Darko Stefanovski,&nbsp;Youwen You,&nbsp;Rachel Proctor,&nbsp;Kasey Seizova,&nbsp;Amritha Mallikarjun,&nbsp;Cynthia M. Otto","doi":"10.1111/jvp.13515","DOIUrl":"10.1111/jvp.13515","url":null,"abstract":"<p>A randomized, blinded, placebo-controlled crossover study was performed with eight professional working dogs to evaluate the pharmacokinetics and pharmacodynamics of three opioid reversal agents. Following sedation with 1 mg kg⁻¹ methadone HCl IV, dogs were randomly assigned to receive naloxone, naltrexone, or nalmefene at 0.1 mg kg⁻¹ IM, or saline (0.1 mL kg⁻¹). Sedation scores and vital signs were obtained for 6 h, and blood samples were obtained for 72 h. Across all groups and phases, the mean sedation score prior to methadone was 0.93/14, and prior to reversal/placebo was 11.45/14. Mean sedation scores 1 min post reversal/placebo were 7.6, 7.4, 8.1, and 10.6; and at 5 min were 2.2, 1.9, 1.9, and 11.8 for nalmefene, naloxone, naltrexone, and saline, respectively. Dogs with a sedation score ≥ 10/14 at 20 min after reversal/placebo were administered 0.1 mg kg⁻¹ of naloxone IM and included all dogs that received saline. The reversal agents significantly decreased sedation scores within 5 min (<i>p</i> &lt; 0.001) and reversal was maintained for the duration of the study. A previously undetected slower terminal elimination phase was observed for all analytes between 24 and 72 h; however, future studies with additional time points between 6 and 24 h are needed to generate pharmacokinetic estimates for this phase. These reversal agents may be useful for treating sedation in professional working dogs exposed to opioids prior to seeking veterinary care. Pharmacological differences between methadone and higher potency opioids (fentanyl and its derivatives) preclude interpretation of these findings to non-methadone opioids, and further studies are needed.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 5","pages":"359-367"},"PeriodicalIF":1.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Planned Approach and Implementation of Pharmacology Teaching in the Bachelor's Veterinary Nursing Programme in Sweden.","authors":"Lena Olsén, Ann-Christin Blomkvist","doi":"10.1111/jvp.13513","DOIUrl":"https://doi.org/10.1111/jvp.13513","url":null,"abstract":"<p><p>Veterinary Nurses play a key role in handling drugs and perform medication treatments, thus pharmacological knowledge is essential. The veterinary nurses' role varies widely worldwide but does not include the prescription of drugs. Nevertheless, pharmacology is a complex subject within veterinary nursing education and for the registered veterinary nurse in practice. In this article, we describe and discuss the pedagogical questions \"what, why, and how\" of teaching pharmacology to undergraduate veterinary nurses implemented in the Veterinary Nursing programme in Sweden. The program has undergone vast changes with classes increasing from 40 to 120 students during the last decade. The progression in the program is presented as intended learning objectives, the teaching and learning activities, and the assessment tasks in each course concerning pharmacology. The procedure of several student-activating pedagogical methods is presented. The use of students' evaluations to assess the education, in line with student-centered education, is described. This information can be useful for veterinary nursing program directors, course leaders, administrators, or teachers considering undertaking curricular changes.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063862","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":"Investigating the Pharmacokinetics and Efficacy of Intramammary Ceftiofur Hydrochloride in Prevention of Udder Inflammation in Non-Lactating Dairy Heifers","authors":"Ranee A. Miller,&nbsp;Geof W. Smith,&nbsp;Jennifer L. Halleran,&nbsp;Derek M. Foster,&nbsp;Ronald E. Baynes","doi":"10.1111/jvp.13512","DOIUrl":"10.1111/jvp.13512","url":null,"abstract":"<p>Mastitis is the most burdensome concern for the dairy cattle industry. Antimicrobials are often prophylactically administered to dairy cows at dry-off to reduce the risk of intramammary infection during the dry period and subsequent lactation. Mastitis incidence has increased in dairy heifers after calving, leading to extralabel drug use of various dry cow products, including intramammary ceftiofur hydrochloride. However, the pharmacokinetics and efficacy of this application have yet to be studied. This study aimed to compare the pharmacokinetics and efficacy following no treatment, a non-antimicrobial teat sealant, or a single dose of intramammary ceftiofur given at 21 or 14 days before expected calving. We hypothesized that milk collected following dosing would contain drug residues below the FDA tolerance of 100 ng/mL by calving, and heifers within the ceftiofur treatment groups would have lower somatic cell counts (SCCs) than heifers in the teat sealant and nontreatment control groups. Following treatment or no treatment of 24 prepartum heifers, milk samples were collected until 21 days after calving. Somatic cell counts and ceftiofur concentrations were assessed utilizing a cell counter and UPLC/MS detection, respectively. Ceftiofur administration did not significantly reduce SCCs compared to other groups by days 7, 14, or 21. For heifers treated 14 and 21 days prior to calving, milk had a maximum ceftiofur concentration of 8.14 ± 6.24 and 4.20 ± 5.07 ng/mL 48 h into lactation, respectively. The minimal ceftiofur concentrations in milk collected from these heifers indicate that administration of ceftiofur 14 or 21 days before calving is unlikely to lead to violative residues. However, it is essential that regional regulations regarding the use of ceftiofur are adhered to.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 4","pages":"280-288"},"PeriodicalIF":1.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13512","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Vatinoxan on the Concentrations of Medetomidine, Midazolam, and Fentanyl in Central Nervous System After Subcutaneous Co-Administration in Rats","authors":"Juhana Honkavaara,&nbsp;Emily Lindh,&nbsp;Anna Meller,&nbsp;Karoliina Alm,&nbsp;Marja R. Raekallio,&nbsp;Pernilla Syrjä","doi":"10.1111/jvp.13514","DOIUrl":"10.1111/jvp.13514","url":null,"abstract":"<p>Our aim was to investigate whether vatinoxan, a peripherally acting alpha₂-adrenoceptor antagonist, would affect the concentrations of medetomidine, midazolam, and fentanyl in the central nervous system after subcutaneous co-administration. Twelve healthy male Wistar rats, aged between 13 and 15 weeks, were used in this study. The animals received one of two subcutaneously administered treatments: medetomidine 0.25 mg/kg, midazolam 2 mg/kg, and fentanyl 0.01 mg/kg (MMF) or MMF with 5 mg/kg of vatinoxan (MMF-V). 15 min later, the sedated rats were humanely euthanized with intravenous pentobarbital. Plasma and tissue, including aliquots of the cortex, thalamus, pons, and lumbar spinal cord, were harvested and analyzed for drug concentrations. The treatments were compared with Bonferroni corrected <i>t</i>-tests after one-way analysis of variance. The concentrations of medetomidine (144 ± 19.4 vs. 107 ± 13.1 ng/g [mean ± 95% confidence interval]) (<i>p</i> = 0.04) and fentanyl (2.3 ± 0.2 vs. 1.7 ± 0.3 ng/g) (<i>p</i> = 0.04) in the cortex were significantly higher in the rats administered MMF-V. Similarly, cortex: plasma drug concentration ratios were significantly higher for medetomidine, midazolam, and fentanyl after MMF-V (<i>p</i> &lt; 0.001 for all). The results confirm that vatinoxan increases early cortical exposure to subcutaneously co-administered medetomidine and fentanyl.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 5","pages":"433-438"},"PeriodicalIF":1.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic–Pharmacodynamic Cutoff Values for Doxycycline in Pigs to Support the Establishment of Clinical Breakpoints for Antimicrobial Susceptibility Testing","authors":"Pierre-Louis Toutain,&nbsp;Alain Bousquet-Melou,&nbsp;Aude A. Ferran,&nbsp;Béatrice B. Roques,&nbsp;Jérôme R. E. del Castillo,&nbsp;Peter Lees,&nbsp;Siska Croubels,&nbsp;Eric Bousquet,&nbsp;Ludovic Pelligand","doi":"10.1111/jvp.13511","DOIUrl":"10.1111/jvp.13511","url":null,"abstract":"<p>This meta-analysis provides a population model of doxycycline (DOXY) disposition in pigs for computation of PK/PD cutoff values corresponding to differing modalities of DOXY administration orally in pigs. This analysis enables establishment of specific clinical breakpoints for the development of antimicrobial susceptibility testing of DOXY in pigs. The meta-analysis of 380 data sets, totaling 3295 plasma concentrations obtained from 300 pigs weighing 8.5–101 kg, was performed using a non-linear mixed effect model. The plasma clearance for a typical 50 kg BW pig was estimated to be 0.259 L/kg/h with a corresponding plasma half-life of 7.33 h. The bioavailability of DOXY administered in feed under field conditions was estimated to be 50%, with a large between-subject variability of 84.8%. The bioavailability of DOXY in solution in drinking water was significantly lower (30.7%) but much less variable, with a between-subject variability of 34.3%. Several dosing schedules (5 to 20 mg/kg per day) for two administration modalities (drinking water vs. food) were simulated to calculate the corresponding PK/PD cutoffs. The highest PK/PD cutoff of 0.50 mg/L was obtained for DOXY administered in feed at 20 mg/kg BW.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 4","pages":"300-317"},"PeriodicalIF":1.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of Alprazolam Into the Milk of Lactating Mares and Subsequent Absorption by Nursing Foals","authors":"Camilla Quattrini,&nbsp;Heather K. Knych,&nbsp;K. Gary Magdesian","doi":"10.1111/jvp.13509","DOIUrl":"10.1111/jvp.13509","url":null,"abstract":"<div>\u0000 \u0000 <p>Alprazolam is used to facilitate mare–foal bonding in aggressive or anxious postpartum mares. In humans, alprazolam crosses the blood–milk barrier, but the amount transferred into milk is minor and compatible with breastfeeding as the relative infant dose is &lt; 10%. Similar data are not available for horses. The aim of this study was to measure alprazolam in serum and milk of mares (milk: serum ratio) administered alprazolam, and to determine alprazolam serum concentrations in nursing foals to estimate the extent of absorption. This was a prospective observational study involving 7 healthy postpartum mares and foals. Mares received alprazolam (0.04 mg/kg PO, q12h) for 6 days. Venous blood and milk samples were collected on days 3,4,5 and 6, just before the next dose, and were used to calculate milk: serum ratios and estimate the extent of absorption of alprazolam by foals. A validated liquid chromatography–tandem mass spectrometry assay was used to measure alprazolam and α-hydroxyalprazolam. There were no significant differences in concentrations of alprazolam or α-hydroxyalprazolam in mare serum, milk, or foal serum over time, consistent with steady state and a lack of accumulation. Milk:serum ratios were similar to slightly higher than those reported in humans (median: 0.64; range: 0.42–3.0). Relative foal dose (RFD) based on 12 h concentrations was &lt; 10% in all foals and in 96% of total samples. Foal serum concentrations of alprazolam were 6.6% ± 4.1% of those in mare serum at the same time points. This study shows that milk:serum ratios of alprazolam in mares are variable. Foal serum concentrations and RFD suggest that alprazolam is safe for use in mares with nursing foals.</p>\u0000 </div>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 4","pages":"274-279"},"PeriodicalIF":1.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032380","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":"Single-Dose, Intravenous, and Oral Pharmacokinetics of Isavuconazole in Dogs","authors":"Yishan Kuo,&nbsp;Zhong Li,&nbsp;Lauren E. Forsythe,&nbsp;Jennifer M. Reinhart","doi":"10.1111/jvp.13510","DOIUrl":"10.1111/jvp.13510","url":null,"abstract":"<p>Isavuconazole, a triazole antifungal used in humans for invasive fungal infections, may be effective for treating canine fungal infections, although data on its use in dogs is limited. This study aimed to determine the pharmacokinetics and safety of a single dose of isavuconazole in dogs, administered both intravenously and orally. Six healthy dogs received 186 mg isavuconazonium sulfate in a crossover design, with blood samples collected over 28 days and an 8-week washout period. Plasma isavuconazole and isavuconazonium concentrations were measured by liquid chromatography/mass spectrometry, and pharmacokinetic parameters were determined by non-compartmental analysis. Isavuconazole was well tolerated, with key findings including intravenous clearance at 350 ± 112 mL/kg/h, volume of distribution at steady state at 9.8 ± 4.5 L/kg, and a terminal half-life of 90 ± 44 h. For oral administration, the maximum concentration was 0.60 ± 0.27 μg/mL, time to maximum concentration was 6.73 ± 2.45 h, terminal half-life was 125 ± 80 h, and the area under the curve was 7.44 ± 2.39 μg h/mL. Oral bioavailability was 81.4% ± 12.8%. These results suggest isavuconazole has a long half-life in dogs and is well absorbed orally when administered in the fasted state. Further studies are warranted to establish a therapeutic regimen in dogs.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 4","pages":"234-240"},"PeriodicalIF":1.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Bioavailability of Single-Dose Intramuscular and Intravenous Administration of Thiafentanil in Goats (Capra hircus)","authors":"Judith T. Christie,&nbsp;Mieghan Bruce,&nbsp;Silke Pfitzer,&nbsp;Liesel Laubscher,&nbsp;Jacobus P. Raath,&nbsp;Michael Laurence,&nbsp;Tracy Kellermann,&nbsp;Andrew P. Woodward","doi":"10.1111/jvp.13507","DOIUrl":"10.1111/jvp.13507","url":null,"abstract":"<p>Thiafentanil is a popular opioid agonist used for wildlife chemical immobilisation. Its effects are quickly and completely reversed by the antagonist naltrexone. Successful wildlife immobilisations using thiafentanil have been documented in a variety of wildlife species globally. The aim of this study was to describe the single-dose intramuscular (IM) and intravenous (IV) pharmacokinetics of thiafentanil in goats at a dose of 90 μg/kg using a single cross-over study. The IM dose was administered in the left <i>Vastus lateralis.</i> Plasma samples were collected up to 120 min after thiafentanil administration from two female and eight male adult goats. Samples were analysed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Pharmacokinetic parameters from one and two-compartment models were estimated via a Bayesian approach. The two-compartment model was preferred overall. The estimated bioavailability was 0.677 (90% Crl: 0.542–0.888), absorption rate constant (<i>k</i>_<i>a</i>) was 0.058 1/min (90% Crl: 0.045–0.115) and clearance was 29.0 mL/min/kg (90% Crl: 23.7–36.3) from this model. This study provides key pharmacokinetic data on thiafentanil, supporting a two-compartment model and offering insights into its absorption, bioavailability, and clearance when used for wildlife immobilisation.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 4","pages":"289-299"},"PeriodicalIF":1.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiparasitic Collars: Concentration Levels of Imidacloprid and Flumethrin in Dog Fur Suggest Low Toxicity Risks for Adult Humans","authors":"Margaux Buisson,&nbsp;Laurine Dumas,&nbsp;Célia Gouffran,&nbsp;Eloïse C. Déaux,&nbsp;Laurent Rougier,&nbsp;Sylvia Masson","doi":"10.1111/jvp.13508","DOIUrl":"10.1111/jvp.13508","url":null,"abstract":"<div>\u0000 \u0000 <p>Seresto by Elanco (formerly Bayer Animal Health) is a collar for cats and dogs that provides long-lasting antiparasitic protection through the gradual release of imidacloprid and flumethrin onto the animal's skin. Although the EPA has deemed Seresto safe, their assessment is based on laboratory data, which may not fully reflect real-world exposure. Furthermore, recent reports of over 900 adverse human health events between 2012 and 2022 underscore the need for further safety investigations. We measured these chemicals' concentrations from the fur of eight dogs over 9 months to evaluate how daily interactions with pets could expose humans to toxic levels. Flumethrin was mostly undetectable, and imidacloprid levels were well below the toxicity threshold, suggesting low risks. However, factors like cumulative exposure and individual characteristics warrant consideration. Concentration levels were highest right after collar application, potentially reaching up to 11.6% of an 8 kg child's acceptable daily intake. We recommend limiting prolonged contact with pets, especially for young children, in the first 48 h post-application. We detected residual imidacloprid prior to collar application and 1 month after removal, raising questions as to the potential contamination risks that roaming pets could pose to ecosystems, given the known environmental impacts of these chemicals.</p>\u0000 </div>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 4","pages":"250-259"},"PeriodicalIF":1.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657617","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 Ampicillin-Sulbactam in Azotemic and Non-Azotemic Dogs","authors":"Zhe Wang,&nbsp;Sarah Shropshire,&nbsp;Daniel Gustafson,&nbsp;Samantha Fedotova,&nbsp;Amanda Diaz,&nbsp;Nida Chornarm,&nbsp;Joshua B. Daniels,&nbsp;Jessica Quimby,&nbsp;Kristin M. Zersen","doi":"10.1111/jvp.13506","DOIUrl":"10.1111/jvp.13506","url":null,"abstract":"<div>\u0000 \u0000 <p>Previous research has shown that azotemic dogs have a lower clearance and higher drug plasma concentrations of ampicillin compared to healthy dogs. The objective of this study was to determine the pharmacokinetics of ampicillin-sulbactam after multiple intravenous doses in hospitalized azotemic and non-azotemic dogs. This prospective study included 29 client-owned dogs; 19 azotemic and 10 non-azotemic. Ampicillin-sulbactam was administered at a combined dose of 22 mg/kg intravenously every 8 h for up to 5 days. Blood samples were obtained at baseline (prior to administration of the first dose of ampicillin-sulbactam), and 1-, 4-, and 8-h post-ampicillin-sulbactam administration each day. Plasma ampicillin was measured using LC-MS and non-compartmental pharmacokinetic modeling and dose interval modeling were performed. Plasma ampicillin exposure (azotemic mean 214.5 ug/mL × h ± 110.8, non-azotemic mean 60.3 ± 35.7; <i>p</i> &lt; 0.0009) and half-life (azotemic mean 3.9 h ± 2.4, non-azotemic mean 1.5 h ± 0.3; <i>p</i> &lt; 0.00001) were statistically greater in azotemic dogs compared to non-azotemic dogs. Single dose interval modeling predicted that 100% of azotemic dogs would have &gt; 50% of the dosing interval with plasma concentrations &gt; MIC (MIC = 2) with q12 h dosing and 79% of azotemic dogs would have &gt; 50% of the dosing interval with plasma concentrations &gt; MIC (MIC = 8) with q12 h dosing. Comparatively, 20% of non-azotemic dogs were predicted to have &gt; 50% of the dosing interval with plasma concentrations &gt; MIC (MIC = 2) with q12 h dosing and 0 non-azotemic dogs would have &gt; 50% of the dosing interval with plasma concentrations &gt; MIC (MIC = 8) with q12 h dosing. This study demonstrated that q12-h dosing of ampicillin-sulbactam in azotemic dogs over multiple days of administration is sufficient to reach the PK-PD target (&gt; 50% of dosing interval &gt; MIC) against susceptible bacteria.</p>\u0000 </div>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 4","pages":"241-249"},"PeriodicalIF":1.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605448","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}