Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs

Thirty dogs with spontaneously occurring malignant neoplasms were treated monthly with carboplatin (CBDCA) given as a 30-minute intravenous infusion in a dose escalation study. Twenty-eight dogs were considered evaluable for toxicity. The maximally tolerated dose of CBDCA was conceptually defined as that dose, determined by logistic regression analyses of toxicity data, resulting in a 50% incidence of moderate toxicity (MOD₅₀) or a 5% incidence of severe toxicity (SEV₅). Each designated maximally tolerated dose was calculated for the first course of treatment only and for the first and second courses of treatment combined to estimate cumulative drug toxicity. The MOD₅₀ and SEV₅ for the first treatment course were 340 and 278 mg/M², respectively. MOD₅₀ and SEV₅ values for the first plus second treatment courses were 327 and 231 mg/M², respectively. The nadir of neutrophil and platelet counts occurred approximately 14 days after treatment. The mean neutrophil and platelet values for all dogs experiencing myelosuppression during the first two treatment courses were 1541/μL and 62,600/μL, respectively. Nonparametric pharmacokinetic analysis of plasma CBDCA values suggested that half-life (T_1/2), area-under-the-curve and total body clearance (CL_b) were not dose dependent. Volume of distribution (VD_ss) significantly increased with dose only between 100 and 150 mg/M², not between 150 and 300 mg/M². Dose-independent serum CBDCA pharmacokinetic disposition indicates that detailed investigation of tissue CBDCA distribution would be warranted and may identify novel dosing strategies that could improve the therapeutic index of CBDCA by minimizing toxicity. (Journal of Veterinary Internal Medicine 1993; 7:235–240. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Antimicrobial therapy for gastrointestinal diseases.

Antibiotics will always be needed in horses for many types of infections, but the adverse consequences also must be considered. For the conditions described in this article, there is justification for antibiotic therapy. The intestinal problems that antibiotics can induce are among the risks from their administration to horses. Disruption of the endogenous bacterial population, colitis, and diarrhea are the most common complications from antibiotic therapy.     

一种新的赖氨酸源

猪、禽日粮的传统赖氨酸添加源是盐酸Ｌ 赖氨酸。但是 ,如今有了另一种赖氨酸源 ,这种新赖氨酸源在经济上可比传统的盐酸Ｌ 赖氨酸更为合算。这种新赖氨酸源是一种干燥的颗粒状产品 ,其中含硫酸Ｌ 赖氨酸和发酵副产品 ,由谷氨酸棒状杆菌(Ｃｏｒｙｎｅｂａｃｔｅｒｉｕｍｇｌｕｔａｍｉｃｕｍ)发酵产生 ,产地为美国内布拉斯加州。其商品成品提供 60 %盐酸Ｌ 赖氨酸的赖氨酸替代值。此外 ,其发酵副产品还含有盐酸Ｌ 赖氨酸中不含的其它氨基酸、磷和能量 (表 1 )。美国已用猪和肉鸡对其进行了硫酸Ｌ 赖氨酸和盐酸Ｌ 赖氨酸的比较试验。最近在美…     

Effects of sub-minimum inhibitory concentration antibiotic levels and temperature on growth kinetics and outer membrane protein expression in Mannheimia haemolytica and Haemophilus somnus

The objective of this study was to determine the effects of sub-minimum inhibitory concentrations (sub-MICs) of 2 veterinary antibiotic preparations, chlortetracycline (CTC) and chlortetracycline-sulfamethazine (CTC + SMZ), on growth kinetics and outer membrane protein expression in Mannheimia haemolytica and Haemophilus somnus at normal and febrile body temperatures. Sub-minimum inhibitory concentrations of both antibiotics reduced the growth rates of M. haemolytica and H. somnus. Growth of both species was not inhibited when grown at 41 degrees C compared to 37 degrees C. There was no detectable consistent effect of antibiotic or temperature on outer membrane protein expression for either species. Our study indicates that sub-MIC levels of CTC and CTC + SMZ markedly impair growth of clinical M. haemolytica and H. somnus isolates, potentially allowing more effective host clearance during infection.