Journal of veterinary pharmacology and therapeutics最新文献

{"title":"Evaluation of plasma and urine pharmacokinetics of tranexamic acid for equine medication control","authors":"Yohei Minamijima,&nbsp;Taisuke Kuroda,&nbsp;Takahiro Kamiya,&nbsp;Yu Sone,&nbsp;Ai Wakuno,&nbsp;Hideki Ito,&nbsp;Motoi Nomura,&nbsp;Gary Ngai-Wa Leung,&nbsp;Kenji Kinoshita,&nbsp;Masayuki Yamada","doi":"10.1111/jvp.13407","DOIUrl":"10.1111/jvp.13407","url":null,"abstract":"<p>This study aimed to evaluate the pharmacokinetics (PK) of tranexamic acid (TXA) in horses and estimate its irrelevant plasma and urine concentrations using the pharmacokinetic/pharmacodynamic (PK/PD) approach by applying the Pierre-Louis Toutain model. TXA was intravenously administered to eight thoroughbred mares, and plasma and urine TXA concentrations were quantified by liquid chromatography/tandem mass spectrometry. The quantified data were used to calculate the PK parameters of TXA in horses. The plasma elimination curves were best-fitted to a three-compartment model. Using the Toutain model approach, irrelevant plasma and urine TXA concentrations were estimated to be 0.0206 and 0.997 μg/mL, respectively. The typical values of clearance, steady-state volume of distribution, and steady-state urine-to-plasma ratio were 0.080 L/kg/h, 0.86 L/kg, and 49.0, respectively. The obtained irrelevant concentrations will be useful for establishing relevant regulatory screening limits for effective control of TXA use in horse racing and equestrian sports.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 1","pages":"21-27"},"PeriodicalIF":1.3,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41137416","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":"Depletion of dexamethasone in cattle: Food safety study in dairy and beef cattle","authors":"Al Chicoine,&nbsp;David L. Renaud,&nbsp;Saad S. Enouri,&nbsp;Patricia M. Dowling,&nbsp;Yu Gu,&nbsp;Ron J. Johnson","doi":"10.1111/jvp.13409","DOIUrl":"10.1111/jvp.13409","url":null,"abstract":"<p>Dexamethasone is approved for cattle in Canada for several conditions, but no withdrawal times are currently provided on the approved labels. Recently, the list of Maximum Residues Limits for Veterinary Drugs in Foods in Canada was amended to include dexamethasone. The objectives of this study were to determine the residue depletion profile of dexamethasone after an extra-label dosage regimen in milk of healthy lactating dairy cattle (<i>n</i> = 18) and in edible tissues of healthy beef cattle (<i>n</i> = 16) and to suggest withdrawal intervals. Dexamethasone was administered intramuscularly at 0.05 mg/kg daily for 3 days. Milk samples were collected prior to treatment and every 12 h up to 96 h post-dose. Muscle, liver, kidney, and peri-renal fat tissues were collected from beef cattle at 3, 7, 11, or 15 days post-dose. Dexamethasone analysis was performed by liquid chromatography/mass spectrophotometry. Dexamethasone residues were detected in milk samples up to 36 h. Muscle and fat had no detectable dexamethasone residues while kidney and liver had detectable residues only on day 3 post-dose. A withdrawal interval of 48 h for milk in Canadian dairy cattle and 7 days for meat in Canadian beef cattle are suggested for the dexamethasone treatment regimen most commonly requested to CgFARAD™.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 2","pages":"80-86"},"PeriodicalIF":1.3,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134246","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":"Safety, tolerability and biological responses of Oreochromis niloticus juveniles upon oral oxolinic acid administration","authors":"Thangapalam Jawahar Abraham,&nbsp;Jaykumar Bhagubhai Patel,&nbsp;Avishek Bardhan,&nbsp;Ravindran Rajisha,&nbsp;Satyen Kumar Panda,&nbsp;Prasanna Kumar Patil","doi":"10.1111/jvp.13408","DOIUrl":"10.1111/jvp.13408","url":null,"abstract":"<p>In aquaculture, oxolinic acid (OA) is used as a second-line treatment at 12 mg/kg biomass/day for seven consecutive days. The present study evaluated the biosafety of 21 days of dietary administration of OA at 0, 12, 36, 60 and 120 mg by assessing the growth, biochemical, erythrocytic morphological and histopathological alterations and residue levels in <i>Oreochromis niloticus</i>. A significant dose-dependent reduction in feed intake and biomass and an increase in mortalities and erythrocytic cellular and nuclear changes were recorded. Significant elevations in plasma glucose, creatinine, alkaline phosphatase, alanine transaminase and aspartate transaminase and a decline in calcium and chloride levels were documented. The kidney, liver and intestine histoarchitecture showed mild to marked alterations. The edible tissue OA residues peaked on day 21 and decreased upon cessation of administration in all the dosing groups. The residue levels in the muscle of the recommended dose group were well within the maximum residue limit set by the European Medicines Evaluation Agency. Although the current study hinted at the safety and tolerability of OA even during long-term usage in <i>O. niloticus</i> in Indian conditions, care must be exercised for its aquacultural application because of its listing as a critically important medicine for humans.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 2","pages":"121-133"},"PeriodicalIF":1.3,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163010","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":"Disposition kinetics of meloxicam in green sea turtles (Chelonia mydas) after intravenous and intramuscular administrations","authors":"Amnart Poapolathep,&nbsp;Oranee Jongkolpath,&nbsp;Mario Giorgi,&nbsp;Narumol Klangkaew,&nbsp;Napasorn Phaochoosak,&nbsp;Thanaphan Chomcheun,&nbsp;Amornthep Archawakulathep,&nbsp;Saranya Poapolathep","doi":"10.1111/jvp.13406","DOIUrl":"10.1111/jvp.13406","url":null,"abstract":"<p>The pharmacokinetics were described of meloxicam (MLX) in green sea turtles (<i>Chelonia mydas</i>), following a single intravenous (i.v.) and intramuscular (i.m.) administrations at one of two dosages of 0.1 or 0.2 mg/kg body weight (b.w.). The sample of 20 green sea turtles was divided into four groups (<i>n</i> = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at pre-assigned times up to 168 h. MLX in the plasma was cleaned-up and quantified using a validated high-performance liquid chromatography method with UV detection. The concentration of MLX in the experimental green sea turtles with respect to time was pharmacokinetically analyzed using a non-compartment model. MLX plasma concentrations were quantifiable for up to 72 and 120 h after i.v. at dosages of 0.1 and 0.2 mg/kg b.w., respectively, whereas it was measurable for up to 168 h after i.m. administration at both dosages. The long elimination half-life value of MLX (28 h) obtained in green sea turtles after i.v. administration was consistent with the quite slow clearance rate for both dosages. The average maximum concentration (<i>C</i>_max) values of MLX were 1.05 μg/mL and 4.26 μg/mL at dosages of 0.1 and 0.2 mg/kg b.w., respectively, with their elimination half-life values being 37.26 h and 30.64 h, respectively, after i.m. administrations. The absolute i.m. bioavailability was approximately 110%. These results suggested that i.m. administration of MLX at a dosage of 0.2 mg/kg b.w. was likely to be effective for clinical use in green sea turtles (<i>Chelonia mydas</i>). However, further studies are needed to determine the pharmacodynamic properties and clinical efficacy of MLX for the treatment of inflammatory disease after single and multiple dosages.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 1","pages":"54-59"},"PeriodicalIF":1.3,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10262202","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 toltrazuril and its metabolite, toltrazuril sulfone, in suckling piglets following oral and intramuscular administrations","authors":"Ta-Wei Yeh,&nbsp;Tirawat Rairat,&nbsp;Chao-Ming Wang,&nbsp;Ching-Fen Wu,&nbsp;Szu-Wei Huang,&nbsp;Chi-Chung Chou,&nbsp;Hung-Chih Kuo","doi":"10.1111/jvp.13405","DOIUrl":"10.1111/jvp.13405","url":null,"abstract":"<p>Toltrazuril (TZR) is currently the only registered chemotherapeutic drug in the European Union for the treatment of <i>Cystoisospora suis</i>. This study investigated the comparative pharmacokinetics and tissue concentration-time profiles of TZR and its active metabolite, toltrazuril sulfone (TZR-SO₂), after oral (per os, p.o.) and intramuscular (i.m.) administration to suckling piglets. Following a single administration of TZR orally at 50 mg/piglet or intramuscularly at 45 mg/piglet, higher concentrations of TZR and TZR-SO₂ were observed in all three investigated tissues after p.o. administration. The mean TZR concentration in serum peaked at 14 μg/mL (34.03 h) and 5.36 μg/mL (120 h), while TZR-SO₂ peaked at 14.12 μg/mL (246 h) and 9.92 μg/mL (330 h) after p.o. and i.m. administration, respectively. TZR was undetectable in the liver after p.o. administration (18 days) and in the jejunum (24 days) after i.m. injection, while TZR-SO₂ was still detectable in all three tissues after 36 days regardless of administration routes. This study showed that p.o. formulation exhibited faster absorption and higher serum/tissue TZR/TZR-SO₂ concentrations than i.m. formulation. Both formulations generated sufficient therapeutic concentrations in the serum and jejunum, and sustained enough time to protect against <i>Cystoisospora suis</i> infection in the piglets.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 1","pages":"36-47"},"PeriodicalIF":1.3,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012266","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 a single oral dose of grapiprant in juvenile pigs (Sus scrofa domestica)","authors":"Stephanie Kleine,&nbsp;Chiara E. Hampton,&nbsp;Christopher Smith,&nbsp;Genevieve Bussieres,&nbsp;Pierre-Yves Mulon,&nbsp;Reza Seddighi,&nbsp;Sherry Cox,&nbsp;Joe Smith","doi":"10.1111/jvp.13402","DOIUrl":"10.1111/jvp.13402","url":null,"abstract":"<p>Both pet and research pigs can suffer from some degree of pain from surgery, injuries, or osteoarthritis (OA). Despite this, there is a paucity of data on safe and effective analgesia agents in pigs. Grapiprant is an EP4 antagonist that blocks the action of the pro-inflammatory prostanoid, PGE₂. It has shown efficacy in attenuating pain associated with ovariohysterectomy and OA in dogs. However, there are no data regarding grapiprant in pigs. Therefore, the pharmacokinetic profile of orally administered grapiprant to juvenile pigs (<i>Sus scrofa domestica</i>) was evaluated in this study. Seven juvenile pigs received 12 mg/kg grapiprant orally. Blood was collected from an indwelling jugular catheter using the push–pull method at set timepoints up to 48 hours. Sample analysis was performed with high-performance liquid chromatography. Mean grapiprant plasma concentration was 164.3 ± 104.7 ng/mL which occurred at 0.8 ± 0.3 h. This study demonstrated that grapiprant concentrations consistent with analgesia in dogs were reached at this dosage in pigs. Further studies are needed to evaluate the efficacy of grapiprant in pigs.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"46 5","pages":"269-275"},"PeriodicalIF":1.3,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10140070","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":"Age-related changes in the pharmacokinetics of meloxicam after intravenous administration in sheep","authors":"Devran Coskun,&nbsp;Orhan Corum,&nbsp;Duygu Durna Corum,&nbsp;Gul Cetin,&nbsp;Mehmet Irmak,&nbsp;Hatice Rumeysa Ceyhan,&nbsp;Kamil Uney","doi":"10.1111/jvp.13404","DOIUrl":"10.1111/jvp.13404","url":null,"abstract":"<p>The pharmacokinetics of meloxicam was studied in 1-, 6-, and 12-month-old sheep following a single intravenous (i.v.) dose of 1 mg/kg. The experiments were carried out when the Romanov sheep were 1 month old (7.93 ± 0.91 kg), 6 months old (27.47 ± 4.91 kg), and 12 months old (37.10 ± 3.64 kg). Meloxicam concentration in plasma was determined by high-performance liquid chromatography and the data collected were evaluated by non-compartmental kinetic analysis. Meloxicam was detected in the plasma up to 72 h following i.v. administration in all age groups. The volume of distribution at steady state (V_dss) and total body clearance (Cl_T) were significantly higher in 1-month-old (304.87 mL/kg and 16.57 mL/h/kg) than in 12-month-old (193.43 mL/kg and 10.50 mL/h/kg) sheep. The area under the concentration–time curve from 0 to 72 h value of meloxicam was lower in 1-month-old (58.51 h*μg/mL) compared to 12-month-old (92.59 h*μg/mL) sheep. There was no difference in t_1/2ʎz value in different age groups. The body extraction ratio values for meloxicam ranged from 0.0186 to 0.0719 after i.v. administration in all age groups. Meloxicam showed an increase in plasma concentration and a decrease in V_dss and Cl_T in 12-month-old compared to 1-month-old sheep. Compared to 1-month-old and 12-month-old sheep, there was no difference in these parameters in 6-month-old sheep. Because the age of sheep has an influence on the pharmacokinetics of meloxicam, dosage apparently may need to be adjusted for age.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"46 5","pages":"326-331"},"PeriodicalIF":1.3,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10150506","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":"Cannabidiol and cannabidiolic acid: Preliminary in vitro evaluation of metabolism and drug–drug interactions involving canine cytochrome P-450, UDP-glucuronosyltransferase, and P-glycoprotein","authors":"Michael H. Court,&nbsp;Katrina L. Mealey,&nbsp;Neal S. Burke,&nbsp;Tania Perez Jimenez,&nbsp;Zhaohui Zhu,&nbsp;Joseph J. Wakshlag","doi":"10.1111/jvp.13403","DOIUrl":"10.1111/jvp.13403","url":null,"abstract":"<p>Phytocannabinoid-rich hemp extracts containing cannabidiol (CBD) and cannabidiolic acid (CBDA) are increasingly being used to treat various disorders in dogs. The objectives of this study were to obtain preliminary information regarding the in vitro metabolism of these compounds and their capacity to inhibit canine cytochrome P450 (CYP)-mediated drug metabolism and canine P-glycoprotein-mediated transport. Pure CBD and CBDA, and hemp extracts enriched for CBD and for CBDA were evaluated. Substrate depletion assays using pooled dog liver microsomes showed CYP cofactor-dependent depletion of CBD (but not CBDA) and UDP-glucuronosytransferase cofactor-dependent depletion of CBDA (but not CBD) indicating major roles for CYP and UDP-glucuronosytransferase in the metabolism of these phytocannabinoids, respectively. Further studies using recombinant canine CYPs demonstrated substantial CBD depletion by the major hepatic P450 enzymes CYP1A2 and CYP2C21. These results were confirmed by showing increased CBD depletion by liver microsomes from dogs treated with a known CYP1A2 inducer (β-naphthoflavone) and with a known CYP2C21 inducer (phenobarbital). Cannabinoid-drug inhibition experiments showed inhibition (IC₅₀ = 4.6–8.1 μM) of tramadol metabolism via CYP2B11-mediated <i>N</i>-demethylation (CBD and CBDA) and CYP2D15-mediated <i>O</i>-demethylation (CBDA only) by dog liver microsomes. CBD and CBDA did not inhibit CYP3A12-mediated midazolam 1′-hydroxylation (IC₅₀ &gt; 10 μM). CBD and CBDA were not substrates or competitive inhibitors of canine P-glycoprotein. Results for cannabinoid-enriched hemp extracts were identical to those for pure cannabinoids. These in vitro studies indicate the potential for cannabinoid–drug interactions involving certain CYPs (but not P-glycoprotein). Confirmatory in vivo studies are warranted.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 1","pages":"1-13"},"PeriodicalIF":1.3,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828268","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":"Determination of temporal changes in hepatic drug-oxidizing capacity using plasma metabolite/caffeine ratios in non-pregnant and pregnant goats","authors":"Feray Altan,&nbsp;Sakine Ulkum Cizmeci,&nbsp;Ayse Merve Kose,&nbsp;Orhan Corum,&nbsp;Kamil Uney","doi":"10.1111/jvp.13401","DOIUrl":"10.1111/jvp.13401","url":null,"abstract":"<p>Caffeine (CF) is a metabolic probe drug used in the determination of the hepatic drug-oxidizing capacity. The aim of this study was to investigate temporal changes in the hepatic drug-oxidizing capacity using plasma metabolite/CF ratios in non-pregnant goats (<i>n</i> = 11) and pregnant goats (<i>n</i> = 23). CF (5 mg/kg, intravenous) was administered in six periods (Period 1–6) with 45 days between two periods. The plasma levels of CF and its metabolites, theophylline (TP), theobromine (TB) and paraxanthine (PX), were determined by HPLC-UV. To evaluate hepatic drug-oxidizing capacity in terms of enzymes that play a role in CF metabolism, the plasma metabolic ratios including TB/CF, PX/CF, TP/CF and TB + PX + TP/CF were determined at 10 h following CF administration. Plasma metabolite/CF ratios were similar between non-pregnant and pregnant goats. However, plasma metabolite/CF ratios in Period 3 (45 days in pregnant goats) were significantly higher than those other periods in both pregnant and non-pregnant goats. The effect of pregnancy may not be observed on drugs that are substrates of enzymes involved in CF metabolism in goats.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 1","pages":"28-35"},"PeriodicalIF":1.3,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9761025","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":"Pharmacokinetic disposition of marbofloxacin after intramuscular administration in estuarine crocodiles (Crocodylus porosus)","authors":"Mona Yalong,&nbsp;Saranya Poapolathep,&nbsp;Mario Giorgi,&nbsp;Kraisiri Khidkhan,&nbsp;Narumol Klangkaew,&nbsp;Napasorn Phaochoosak,&nbsp;Narongsak Chaiyabutr,&nbsp;Tara Wongwaipairoj,&nbsp;Amnart Poapolathep","doi":"10.1111/jvp.13400","DOIUrl":"10.1111/jvp.13400","url":null,"abstract":"<p>To date, the pharmacokinetics of fluoroquinolones in estuarine crocodiles (<i>Crocodylus porosus</i>) have been reported for enrofloxacin but not for marbofloxacin (MBF), which is a broad-spectrum antibiotic used only in veterinary medicine. This study investigated the pharmacokinetics of MBF after intramuscular administration at two difference dosages (2 and 4 mg/kg body weight) in estuarine crocodiles and estimated pharmacokinetic/pharmacodynamic (PK/PD) surrogate parameters for the optimization of dosage regimens. Ten treated estuarine crocodiles were divided into two groups (<i>n</i> = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at assigned times up to 168 h. MBF plasma samples were cleaned up using liquid–liquid extraction and analyzed using a validated high-performance liquid chromatography method with fluorescence detection. A non-compartment approach was used to fit the plasma concentration of MBF vs time curve for each crocodile. The plasma concentrations of MBF were quantifiable for up to 168 h in both groups. The elimination half-life values of MBF were long (33.99 and 39.28 h for 2 and 4 mg/kg, respectively) with no significant differences between the groups. The average plasma protein binding of MBF was 30.85%. According to the surrogated PK/PD parameter (AUC_0–24-to-MIC ratio &gt;100–125), the 2 and 4 mg/kg dosing rates should be effective for bacteria with MIC values lower than 0.125 μg/mL and 0.35 μg/mL, respectively.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 1","pages":"48-53"},"PeriodicalIF":1.3,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10071536","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}