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Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs   总被引:1,自引:1,他引:0  
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 (T1/2), area-under-the-curve and total body clearance (CLb) were not dose dependent. Volume of distribution (VDss) 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.)  相似文献   
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This review summarizes a number of recent reports in several areas of lipid and lipoprotein metabolism. Absorption of dietary lipids, cholesterol synthesis, and biliary cholesterol metabolism are mentioned only briefly to be complete. Comparative aspects of lipoprotein metabolism, however, are detailed in an effort to integrate the myriad metabolic events which characterize these important lipid transport particles. Where comparative information is known, those aspects of lipoprotein metabolism that may be protective against atherogenesis in certain mammalian species are also described. Efforts to understand atherogenic resistance comparatively in animals lends a better understanding of the metabolic events leading to coronary artery disease in humans. They also provide an important basis for understanding lipid metabolism in numerous veterinary species.  相似文献   
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An interspecies pharmacokinetic model for gentamicin was developed using the mixed effects modeling approach and serum disposition data obtained from the Food Animal Residue Avoidance Databank (FARAD). Data that met a priori quality criteria was obtained from the database and analysed using the traditional double logarithmic analysis and the mixed effects modeling approach. Body weight, brain weight and fever were the covariates of interest in our study. Population pharmacokinetic models across species were developed and validated with swine data. The parameter volume of distribution was modeled as a function of body weight. The total clearance was initially modeled as a function of body weight. The predictability performance of the model improved dramatically when the parameter brain weight was included in the covariate model for clearance. This was a surprising finding worthy of further study. The covariate fever seemed to influence the magnitude of the volume of distribution, although the scarcity of data pertaining to diseased animals makes this finding uncertain. We conclude that the pharmacokinetic characteristics of drugs such as gentamicin, can be predicted across species using a population pharmacokinetics modeling approach, and that clinical features that affect species in a similar manner can be also explored in this fashion.  相似文献   
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The effects of different doses and dosage regimens on gentamicin pharmacokinetics and tissue residues were determined. Five groups of 12 sheep each were given gentamicin IM: group I, 2 mg of gentamicin sulfate/kg once; group II, 6 mg/kg once; group III, 18 mg/kg once; group IV, 6 mg/kg every 24 hours for 3 doses; and group V, 2 mg/kg every 8 hours for 9 doses. Serum concentrations were determined serially until sheep were killed and necropsied. Three sheep from each group were killed at 1, 4, 8, and 12 days after the last dose was administered. Renal cortex, renal medulla, liver, spleen, lung, skeletal muscle, and skeletal muscle at the injection site were assayed for gentamicin. An exponential equation was fitted to the serum concentrations, and various pharmacokinetic variables were determined. Serum clearance tended to increase as the single dose increased (P = 0.0588). Steady-state volume of distribution increased as the single dose was increased (P less than 0.05). Renal cortex contained the highest concentration of gentamicin which decreased in a biexponential manner. Concentrations in all tissues, except the injection site, were dependent upon the amount of the total dose, not the size of the injected dose (P less than 0.05). Concentrations at the injection site were up to 29 micrograms/g of tissue at 1 day after the last dose was given and were dependent upon the amount of total dose from multiple injections, not on the amount of each injected dose (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
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Objective To compare different methods for assessing the compliance of veterinary clients administering medication to their dogs.
Procedure Thirty-one owners whose dogs were prescribed amoxycillin-clavulanate, twice and thrice daily, for a duration of five to seven days were recruited from three Sydney veterinary hospitals. Compliance was assessed by electronic monitoring devices, return medication counts, client self-reports and veterinarians' estimation of likely compliance.
Results Electronic monitoring showed owners administered on average 84% (range 7 to 104%) of prescribed medication to their dogs. Both return medication counts and client self-reports tended to overestimate therapeutic compliance when compared with electronic monitoring. When questioned, the majority of owners (71%) claimed perfect compliance with the prescribed regimen. No correlation was found between veterinarians' estimates of owner compliance and that assessed electronically.
Conclusion Electronic monitoring provided valuable information on dose timing and variation, but proved costly and difficult to employ in veterinary practice. Simplicity and low cost of return medication counts makes this method attractive for use in veterinary compliance studies. Client self-reports reliably detected some noncompliers and permitted identification of individual problems or errors. For practical purposes a combination of return medication counts and client self-reports may have merit in future veterinary compliance studies.  相似文献   
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Identification of plaque spirochetes from dogs is rare and no studies to date report cultivation of canine or feline plaque spirochetes. Plaque samples obtained from canine and feline patients were cultured in broth media. Spirochetes cultured were subjected to microscopic evaluation and were cloned on a solid medium. The clones were provisionally identified using species-specific PCR for treponema isolated from human plaque. Canine spirochete clones included Treponema denticola, T. socranskii ssp., T. vincentii, T. maltophilum, T. medium, and T. pectinovorum. Feline clones included T. maltophilum and T. socranskii. Non-amplified clones may represent novel treponemes. Future studies will be aimed at comparison of the spirochetes present in dogs and cats with or without periodontal disease.  相似文献   
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Pharmacokinetics and metabolic inertness of doxycycline in young pigs   总被引:5,自引:0,他引:5  
The disposition of doxycycline hyclate after IV administration of 20 mg/kg of body weight was studied in 6 pigs. Median elimination half-life, estimated in 4 pigs, was 3.92 hours. Mean (+/- SEM) total body clearance was 1.67 +/- 0.18 ml/min/kg, and mean apparent volume of distribution at steady state was 0.53 +/- 0.04 L/kg. In 2 pigs, secondary peaks in the logarithmic serum concentration-time profile suggested discontinuous enterohepatic cycling, and precluded using these pigs in the pharmacokinetic analysis. The extent of doxycycline binding to serum protein was 93.1 +/- 0.2%. Serum or urine from 3 of the pigs was analyzed by use of photodiode array detection and mass spectrometry of a high-performance liquid chromatographic column effluent. These procedures documented lack of doxycycline biotransformation in pigs. It is concluded that, despite an elimination half-life shorter than that reported in other species, doxycycline may be a valuable antimicrobial drug for use in swine practice, pending the development of appropriate formulations.  相似文献   
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