Journal of veterinary pharmacology and therapeutics最新文献

{"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}

{"title":"Pharmacokinetics of oral tapentadol in cats","authors":"J. Lakritz,&nbsp;T. K. Aarnes,&nbsp;B. Alva,&nbsp;J. Howard,&nbsp;G. Magnin,&nbsp;P. Lerche,&nbsp;B. Kukanich","doi":"10.1111/jvp.13399","DOIUrl":"10.1111/jvp.13399","url":null,"abstract":"<p>To evaluate pharmacokinetics of one dose of tapentadol hydrochloride orally administered to cats. Prospective experimental study. Five healthy adult mixed-breed cats. Each cat received 18.8 ± 1.0 mg/kg tapentadol orally. Venous blood samples were collected at time 0 (immediately prior to administration of tapentadol) 1, 2, 5, 10, 15, 30, 45, 60, 90 min, and 2, 4, 8, 12 to 24 h after drug administration. Plasma tapentadol concentrations and its metabolites were determined using ultra-performance liquid chromatography–tandem mass spectrometry. Geometric mean T_max of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 2.3, 7.0, 6.0, and 4.6 h, respectively. Mean <i>C</i>_max of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 637, 66, 1134, and 15,757 ng/mL, respectively, after administration. Mean half-life of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 2.4, 4.7, 2.9, and 10.8 h. The relative exposure of tapentadol and its metabolites were tapentadol 2.65%, desmethyltapentadol 0.54%, tapentadol-O-glucuronide 6.22%, and tapentadol-O-sulfate 90.6%. Tapentadol-O-sulfate was the predominant metabolite following the administration of oral tapentadol in cats. Further studies are warranted to evaluate the association of analgesia with plasma concentrations of tapentadol.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 1","pages":"14-20"},"PeriodicalIF":1.3,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10051305","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":"Disposition kinetics of robenacoxib following intravenous and oral administration in geese (Anser anser domesticus)","authors":"Charbel Fadel,&nbsp;Beata Łebkowska-Wieruszewska,&nbsp;Andrzej Lisowski,&nbsp;Seavchou Laut,&nbsp;Amnart Poapolathep,&nbsp;Mario Giorgi","doi":"10.1111/jvp.13398","DOIUrl":"10.1111/jvp.13398","url":null,"abstract":"<p>Robenacoxib (RX) is a veterinary cyclooxygenase-2 selective inhibitor drug. It has never been tested on birds and is only labelled for use in cats and dogs. The purpose of this study was to assess its pharmacokinetics in geese after single intravenous (IV) and oral (PO) administrations. Four-month healthy female geese (<i>n</i> = 8) were used. Geese were subjected to a two-phase, single-dose (2 mg/kg IV, 4 mg/kg PO), open, longitudinal study design with a four-month washout period between the IV and the PO phases. Blood was collected from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 h. Plasma RX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analysed using ThothPro™ 4.3 software in a non-compartmental approach. Following IV administration, terminal elimination half-life, volume of distribution, and total clearance were 0.35 h, 0.34 L/kg, and 0.68 L/h/kg, respectively. For the PO route, the mean peak plasma concentration was 6.78 μg/mL at 0.50 h. The <i>t</i>1/2<i>λz</i> was very short and significantly different between the IV and PO administrations (0.35 h IV vs. 0.99 h PO), suggesting the occurrence of a flip-flop phenomenon. The Cl values corrected for the <i>F</i>% were significantly different between IV and PO administrations. It might have been a consequence of the longitudinal study design and the altered physiological and environmental conditions after a 4-month washout period. The absolute oral <i>F</i>% computed with the AUC method surpassed 150%, but after normalizing it to <i>t</i>1/2<i>λz</i>, it was 46%. In conclusion, the administration of RX might not be suitable for geese, due to its short <i>t</i>1/2<i>λz</i>.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"46 6","pages":"413-420"},"PeriodicalIF":1.3,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9982948","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":"P9 | Pharmacokinetics of lincomycin in laying hens and its residue profiles in egg and plasma","authors":"","doi":"10.1111/jvp.13288","DOIUrl":"10.1111/jvp.13288","url":null,"abstract":"","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"46 S1","pages":"89"},"PeriodicalIF":1.3,"publicationDate":"2023-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42967064","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":"O4 | Pharmacokinetics of bupivacaine after bilateral maxillary and inferior alveolar nerve blocks in adult cats","authors":"","doi":"10.1111/jvp.13170","DOIUrl":"10.1111/jvp.13170","url":null,"abstract":"","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"46 S1","pages":"29"},"PeriodicalIF":1.3,"publicationDate":"2023-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45626995","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":"O85 | Antibacterial activity of propyl gallate in combination with orbifloxacinagainst E. coli in an in vitro pharmacodynamic model","authors":"","doi":"10.1111/jvp.13251","DOIUrl":"10.1111/jvp.13251","url":null,"abstract":"","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"46 S1","pages":"70"},"PeriodicalIF":1.3,"publicationDate":"2023-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48516109","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":"P67 | Determination of the PK/PD cut-off of oxytetracycline in cattle using the VetCAST method to support the establishment of a clinical breakpoint for antimicrobial susceptibility testing","authors":"","doi":"10.1111/jvp.13346","DOIUrl":"10.1111/jvp.13346","url":null,"abstract":"","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"46 S1","pages":"117-118"},"PeriodicalIF":1.3,"publicationDate":"2023-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43453119","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}