Michelle P. Buckley, Kristen P. Hayman, Laura Burns, Dwayne Schrunk, Patrick J. Gorden
{"title":"奶山羊乳房内注射长效头孢匹林和氯唑西林的药代动力学。","authors":"Michelle P. Buckley, Kristen P. Hayman, Laura Burns, Dwayne Schrunk, Patrick J. Gorden","doi":"10.1111/jvp.13445","DOIUrl":null,"url":null,"abstract":"<p>Determining the pharmacokinetics of intramammary antimicrobials in goats can assist in predicting appropriate meat and milk withdrawal intervals for drugs that are effective at treating subclinical mastitis due to non-aureus <i>Staphylococci</i> during the dry period. Twenty-four healthy, lactating does were enrolled in this study. Half were administered 300 mg of cephapirin benzathine (ToMORROW, Boehringer Ingelheim Vetmedica, Duluth, GA) via intramammary infusion into each half of the udder. The remaining does had 500 mg cloxacillin benzathine (Orbenin DC, Merck & Co., Rahway, NJ) administered per half. Plasma was collected before treatment and for 7 days post-treatment followed by analysis via liquid chromatography with tandem mass spectroscopy. Pharmacokinetic parameters were determined using noncompartmental methods via commercial software (MonolixSuite). The mean maximum concentration (<i>C</i>\n <sub>max</sub>) of cephapirin of 0.073 μg/mL was noted at 7.06 h post-administration (<i>T</i>\n <sub>max</sub>). The area under the plasma concentration curve based on the final sampling point (AUC<sub>last</sub>) was 1.06 h × μg/mL. The mean residence time until the final sampling point (MRT<sub>last</sub>) was 13.55 h. Mean terminal half-life (<i>T</i>\n <sub>½</sub>) of cephapirin was 6.98 h. In CLOX does, <i>C</i>\n <sub>max</sub> was 0.074 μg/mL with a <i>T</i>\n <sub>max</sub> of 18 h, AUC<sub>last</sub> was 5.71 h × μg/mL, <i>T</i>\n <sub>½</sub> was 77.45 h, and MRT<sub>last</sub> was 65.36 h. Despite both products being formulated with benzathine salts, marked differences were noted in pharmacokinetic parameters including AUC, <i>T</i>\n <sub>1/2</sub>, and MRT<sub>last</sub>. This data will be used to plan sampling schedules for milk and tissue residue depletion studies for both products.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 5","pages":"396-402"},"PeriodicalIF":1.5000,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13445","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics of long-acting cephapirin and cloxacillin after intramammary administration in dairy goats\",\"authors\":\"Michelle P. Buckley, Kristen P. Hayman, Laura Burns, Dwayne Schrunk, Patrick J. Gorden\",\"doi\":\"10.1111/jvp.13445\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Determining the pharmacokinetics of intramammary antimicrobials in goats can assist in predicting appropriate meat and milk withdrawal intervals for drugs that are effective at treating subclinical mastitis due to non-aureus <i>Staphylococci</i> during the dry period. Twenty-four healthy, lactating does were enrolled in this study. Half were administered 300 mg of cephapirin benzathine (ToMORROW, Boehringer Ingelheim Vetmedica, Duluth, GA) via intramammary infusion into each half of the udder. The remaining does had 500 mg cloxacillin benzathine (Orbenin DC, Merck & Co., Rahway, NJ) administered per half. Plasma was collected before treatment and for 7 days post-treatment followed by analysis via liquid chromatography with tandem mass spectroscopy. Pharmacokinetic parameters were determined using noncompartmental methods via commercial software (MonolixSuite). The mean maximum concentration (<i>C</i>\\n <sub>max</sub>) of cephapirin of 0.073 μg/mL was noted at 7.06 h post-administration (<i>T</i>\\n <sub>max</sub>). The area under the plasma concentration curve based on the final sampling point (AUC<sub>last</sub>) was 1.06 h × μg/mL. The mean residence time until the final sampling point (MRT<sub>last</sub>) was 13.55 h. Mean terminal half-life (<i>T</i>\\n <sub>½</sub>) of cephapirin was 6.98 h. In CLOX does, <i>C</i>\\n <sub>max</sub> was 0.074 μg/mL with a <i>T</i>\\n <sub>max</sub> of 18 h, AUC<sub>last</sub> was 5.71 h × μg/mL, <i>T</i>\\n <sub>½</sub> was 77.45 h, and MRT<sub>last</sub> was 65.36 h. Despite both products being formulated with benzathine salts, marked differences were noted in pharmacokinetic parameters including AUC, <i>T</i>\\n <sub>1/2</sub>, and MRT<sub>last</sub>. 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Pharmacokinetics of long-acting cephapirin and cloxacillin after intramammary administration in dairy goats
Determining the pharmacokinetics of intramammary antimicrobials in goats can assist in predicting appropriate meat and milk withdrawal intervals for drugs that are effective at treating subclinical mastitis due to non-aureus Staphylococci during the dry period. Twenty-four healthy, lactating does were enrolled in this study. Half were administered 300 mg of cephapirin benzathine (ToMORROW, Boehringer Ingelheim Vetmedica, Duluth, GA) via intramammary infusion into each half of the udder. The remaining does had 500 mg cloxacillin benzathine (Orbenin DC, Merck & Co., Rahway, NJ) administered per half. Plasma was collected before treatment and for 7 days post-treatment followed by analysis via liquid chromatography with tandem mass spectroscopy. Pharmacokinetic parameters were determined using noncompartmental methods via commercial software (MonolixSuite). The mean maximum concentration (Cmax) of cephapirin of 0.073 μg/mL was noted at 7.06 h post-administration (Tmax). The area under the plasma concentration curve based on the final sampling point (AUClast) was 1.06 h × μg/mL. The mean residence time until the final sampling point (MRTlast) was 13.55 h. Mean terminal half-life (T½) of cephapirin was 6.98 h. In CLOX does, Cmax was 0.074 μg/mL with a Tmax of 18 h, AUClast was 5.71 h × μg/mL, T½ was 77.45 h, and MRTlast was 65.36 h. Despite both products being formulated with benzathine salts, marked differences were noted in pharmacokinetic parameters including AUC, T1/2, and MRTlast. This data will be used to plan sampling schedules for milk and tissue residue depletion studies for both products.
期刊介绍:
The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.