Allometric analysis of thiamphenicol disposition among seven mammalian species

The pharmacokinetics of thiamphenicol (TAP), a broad-spectrum antibiotic, was determined in male mice, rats, rabbits, dogs, pigs, sheep and calves. The relationship between the main pharmacokinetic parameters of TAP and body weight (W) was studied across these seven mammalian species, using double-logarithmic plots. The experimental values of volume of distribution (Vss), clearance (Cl) and elimination half-life (t(1/2)beta) were plotted, and extrapolated values were determined from corresponding allometric equations. These parameters were fitted to the following equations: Vss=0.98W0.92, Cl=15.80W0.76 and t(1/2)beta=0.94W0.20, and present good correlation (Vss: r2=0.997, P < 0.001; Cl: r2=0.976, P < 0.001, t(1/2)beta: r2=0.852, P < 0.005), that is expected of a drug eliminated primarily by renal glomerular filtration, with insignificant hepatic metabolism. For the t(1/2)beta, the extrapolated and observed values were similar. The extrapolated values of Cl were close to the experimental values, except for the mouse and pig mean percent error [(M.E.) equal to 62 and 119%, respectively], while the extrapolated and observed values for the Vss were very similar. The comparison between experimental and extrapolated values suggests that it could be possible to extrapolate, with good prediction, the kinetic parameters of this drug for mammalian species, using allometric scaling, except for the species that eliminate the drug by a combination of renal excretion and hepatic metabolism.     

Allometric scaling of marbofloxacin, moxifloxacin, danofloxacin and difloxacin pharmacokinetics: a retrospective analysis

The purpose of this study was to examine the allometric analyses of marbofloxacin, moxifloxacin, danofloxacin and difloxacin using pharmacokinetic data from the literature. The parameters of interest (half-life, clearance and volume of distribution) were correlated across species as a function of body weight using an allometric approach (Y = aWb). Results of the allometric analysis indicated similarity between clearance and volume of distribution as they relate to body weight for all drugs. The elimination half-life was independent of body mass for all fluoroquinolones except moxifloxacin. Results of the analysis suggest that allometric scaling can be used as a tool for predicting pharmacokinetic parameters for fluoroquinolones.     

云杉属植物幼苗的异速比例关系

本研究以云杉属(Picea)8个物种幼苗为例, 通过系统测定其地上、地下呼吸速率, 年均净生产力, 叶生物量以及总生物量, 研究各特性相互间的异速比例关系(Allometric Scaling Relationship)。结果表明, 1)在异化速率方面, 云杉8个物种经温度修正的平均单株地上、地下呼吸速率与相应生物量的异速指数分别为0.876和0.817;2)在同化速率方面, 平均单株叶生物量与平均单株年净生产力的异速指数为1.191, 平均单株叶生物量与其平均总生物量的异速指数为0.940, 两者的异速指数非常接近代谢异速理论对植物小个体代谢速率指数为1的预测;3)不论是植物个体平均地上生物量与地下生物量间的异速指数(1.090), 还是经温度修正的平均单株地上呼吸速率与地下呼吸速率的异速指数(1.168) 均很接近理论预测值1。     

Allometric basis of enrofloxacin scaling in green iguanas

When body size varies greatly, drug disposition can best be described as an allometric function of body weight. Therefore, the allometry of standard metabolic rate (SMR; 3/4 power) and body surface area (BSA; 2/3 power) have been advocated as surrogate markers for the prediction of key pharmacokinetic parameters. The goal of the present study was to examine the allometric basis of pharmacokinetic scaling within a species, green iguanas. Enrofloxacin was administered intravenously to 20 green iguanas (322-3824 g), and noncompartmental analysis was used to calculate standard pharmacokinetic parameters, which were log(10) transformed and regressed against log(10) body weight. The slopes of significant regressions were compared with the values of unity, 3/4, and 2/3. The slope of enrofloxacin total body clearance (Cl) was also compared with the slopes relating SMR and renal Cl of (99m)Tc-diethylenetriamine penta-acetic acid ((99m)DTPA) to body weight in iguanas. Enrofloxacin Cl depended allometrically on body weight with the power of 0.32. The slope of enrofloxacin Cl was significantly less than those of SMR, Cl of (99m)DTPA, and the 2/3 value. Therefore, the relationship between enrofloxacin Cl and body weight does not directly depend on the allometry of BSA, SMR, or renal Cl of (99m)DTPA in iguanas.     

Colorectal plasmacytomas: a retrospective study of nine dogs

Nine cases of colorectal plasmacytomas diagnosed between 1998 and 2001 were reviewed. Treatment consisted of complete surgical resection when possible. Two dogs had multiple plasmacytomas. Two dogs had local recurrence of the tumor at 5 and 8 months after resection. Two dogs were alive at 20 and 23 months with no recurrences at the time of follow-up. The median survival time was 15 months (range 5 to 33 months). Colorectal plasmacytomas are similar to mucocutaneous plasmacytomas, in that they tend to progress slowly and do not recur with complete excision.     

Allometric analysis of ciprofloxacin and enrofloxacin pharmacokinetics across species

The purpose of this study was to examine the allometric analysis of ciprofloxacin and enrofloxacin using pharmacokinetic data from the literature. The pharmacokinetic parameters used were half-life, clearance and volume of distribution. Relationships between body weight and the pharmacokinetic parameter were based on the empirical formula Y = aW(b), where Y is half-life, clearance or volume of distribution, W the body weight and a is an allometric coefficient (intercept) that is constant for a given drug. The exponential term b is a proportionality constant that describes the relationship between the pharmacokinetic parameter of interest and body weight. A total of 21 different species of animals were studied. Results of the allometric analyses indicated similarity between clearance and volume of distribution as they related to body weight for both drugs. Results of the current analyses indicate it is possible to use allometry to predict pharmacokinetic variables of enrofloxacin or ciprofloxacin based on body size of species. This could provide information on appropriate doses of ciprofloxacin and enrofloxacin for all species.     

Allometric scaling of M-mode cardiac measurements in normal adult dogs

Indices for M-mode measurements in dogs usually have been based on the assumption that a linear relationship exists between these measurements and body weight (BW) or body surface area (BSA). The relationships between the geometry of 3-dimensional objects do not support this assumption. The purposes of this study were to retrospectively examine M-mode data from a large number of dogs of varying sizes and breeds that were examined by a large number of ultrasonographers, to use the allometric equation to determine the appropriate BW exponent required to predict these cardiac dimensions, and to determine normal mean values and prediction intervals for common M-mode variables. Linear regression analyses of data from 494 dogs (2.2-95 kg) revealed a good correlation between M-mode measurements and BW after logarithmic transformation of the data (r2 = .55-.88). Most variables were most closely related to an index of body length, BW(1/3), although the exponent that best predicted diastolic and systolic left ventricular wall thicknesses was closer to 0.25. No variable indexed well to BW or BSA. With these data, appropriate mean values and prediction intervals were calculated for normal dogs, allowing veterinarians to correctly and appropriately index M-mode values. The equations developed from this study appear to be applicable to adult dogs of most breeds.     

Modeling and allometric scaling of s(+)-ketoprofen pharmacokinetics and pharmacodynamics: a retrospective analysis

Interspecies scaling of pharmacokinetic (PK) parameters is commonplace in drug development. However, information about proportionality of pharmacodynamic (PD) parameters in different species is scarce. We investigated the feasibility of allometric scaling of PK and PD parameters of s(+)-ketoprofen (sKTP) using the literature data from several animal species. Two different indirect response models were proposed to characterize sKTP inhibitory effects on synthesis of thromboxane B(2) (TXB(2)) and prostaglandin E(2) (PGE(2)). Using the traditional allometric approach, the obtained PK and PD parameters were plotted against body weights (BW) on a log-log scale. For all species, values of systemic clearance (Cl), distribution clearance (Cl(D)), central volume of distribution (V(c)), and volume of distribution at steady-state (V(ss)) were highly correlated (r(2) = 0.89-0.99) with BW. The PD parameters for inhibition of TXB(2) synthesis were poorly correlated with BW (r(2) = 0.25-0.54) while most of the parameters for inhibition of PGE(2) synthesis lacked any correlation (r(2) approximately 0.05). In conclusion, indirect response models adequately described the time course of sKTP inhibitory effects on synthesis of TXB(2) and PGE(2). Allometrical scaling showed PK parameters to change proportionally to BW, whereas PD parameters had limited ranges and were essentially weight independent.     

Disseminated alimentary mycobacteriosis in the horse: a retrospective study of nine cases

This paper summarises the clinical findings of 9 cases of disseminated alimentary mycobacteriosis in horses presented at a Finnish referral equine hospital 2009–2014. Four of 9 horses were Standardbreds and 8/9 horses were male. The median age was 2 years, ranging from 6 months to 15 years. The duration of clinical signs before admission ranged from 2 weeks to 6 months. All horses demonstrated deterioration of the clinical signs after a protracted period of the disease and were finally subjected to euthanasia after poor response to multiple medical therapies. The most common complaints on admission were weight loss and diarrhoea (9/9), pyrexia (7/9), ventral oedema (7/9), lethargy (7/9) and inappetance (6/9). The most common clinicopathological abnormalities were hypoalbuminaemia and hyperfibrinogenaemia, which were present in all horses. Rectal biopsy specimens were examined from 5/9 horses and specimens were stained with Ziehl‐Nielsen (ZN). At rectal biopsy, mild multifocal neutrophilic or mild granulomatous proctitis was recognised in all 5 horses, but the ZN stain for mycobacteria was positive in only one biopsy. A liver biopsy was taken from one horse in which hepatomegaly was observed clinically and revealed marked granulomatous hepatitis with the presence of mycobacteria. The rectal biopsy from this horse was ZN negative. At post mortem examination, chronic, multifocal to coalescing granulomatous typhlocolitis and lymphadenitis were found in all horses with the small intestine less frequently involved. At histopathological examination of post mortem samples, a ZN stain was performed and intracellular acid‐fast bacilli were identified in macrophages and multinucleated giant cells in the large intestine, liver and lymph nodes in 9/9 horses and in the small intestine in 5/9 horses. Mycobacterium avium ssp. hominissuis was isolated in 5/9 horses from post mortem samples.     

Feline dysautonomia in the Midwestern United States: a retrospective study of nine cases

Dysautonomia of domestic animals is pathologically characterized by chromatolytic degeneration of the neurons in the autonomic nervous ganglia that results in clinical signs related to dysfunction or failure of the sympathetic and parasympathetic nervous systems. The exact cause is unknown. It has a poor prognosis among all species reported and no definitive treatment is available currently. To date, most reported feline cases have occurred in the United Kingdom and Scandinavia. The cases reported here highlight the clinical signs, physical examination findings, and results of autonomic nervous system function testing in nine cats with dysautonomia in the US. Feline dysautonomia is uncommon in the US, but may have a regional prevalence, as is seen in dogs with most cases reported in Missouri and Kansas.     

Allometric scaling of echocardiographic measurements in healthy Spanish foals with different body weight

Scaling in biology is usually allometric, and therefore, the size of the heart may be expressed as a power function of body weight (BW). The present research analyses the echocardiographic measurements in 68 healthy Spanish foals weighed between 70 and 347 kg in order to determine the correct scaling exponent for the allometric equation. The echocardiographic parameters measured were: left ventricular internal dimensions (LVID), free wall thickness (LVFWT), interventricular septum thickness (IVST) at systole (s) and diastole (d), EPSS (distance between the point E of the mitral valve and the interventricular septum), and aorta diameters at the level of the aortic valve (AOD), base of valve leaflets (ABS), sinus of Valsalva (ASV) and sino-tubular junction (AJT). Indices of left ventricular performance were calculated. It was found that LVIDd, IVSTs, AOD, and ASV have a relationship to BW raised to 0.300-0.368 power, whereas left ventricular end-diastolic volume and stroke volume scaled to BW raised to 0.731-0.712 power. With these data, appropriate values can be calculated for normal Spanish foals.     

Actinomyces species as a cause of abscesses in nine horses

The characteristics, history, clinical signs, treatment and outcome of nine horses with abscesses caused by Actinomyces species were reviewed. dna sequencing was used to determine the species of one of the isolates. The horses were one to 11 years of age, and the abscesses were most commonly located in the submandibular and retropharyngeal regions. The bacterium was usually cultured as the sole isolate and the horses were most often affected in the autumn. Most of the abscesses were treated with antimicrobials and drainage, but some of them recurred. The horses with submandibular abscesses had residual scar tissue that in some cases did not resolve.     

Allometric scaling, metabolic body size and interspecies comparisons of basal nutritional requirements

The amounts of specific substances needed per day that are generally thought to be nutritionally essential or conditionally important are similar among animal species when expressed per unit of energy consumed or per metabolic body size. Accordingly, a case is made that in addition to basal daily energy utilization, allometric scaling based on metabolic body size (3/4 power of mass or weight in kg) may be used to predict and compare basal nutrient requirements among widely varied species, as well as make comparative toxicological and other biological assessments and predictions. Furthermore, given the increasing evidence for allometric scaling for a broad range of biological phenomena (both empirical and theoretical) there is usually a good biological question to be answered when an organismal process deviates markedly from an allometric scale.     

Allometric analysis of doxycycline pharmacokinetic parameters

Doxycycline serum concentration-time profiles and elimination half-lives in several species were evaluated by allometric techniques. Doxycycline elimination half-life increased with body weight. Interspecies scaling of total or free doxycycline serum concentration-time profiles was possible by use of Dedrick plots with the exception of doxycycline total concentrations in cats. The observed difference in cats was attributed to more extensive binding to plasma proteins.     

Alternaria species infection in nine domestic cats

A case series of nine domestic cats with culture-confirmed Alternaria species infection is presented, with conclusions drawn regarding signalment, clinical signs, treatment and outcome. Middle aged neutered males were over-represented and all presented with cutaneous lesions involving the extremities (nose, pinnae and digits). Lesions were mainly slow-growing, poorly circumscribed nodules or plaques but some also presented as non-healing wounds. A combination of surgical excision with adjunctive medical therapy appeared to be the most successful treatment option but long courses of medical therapy were generally required and recurrence was common.     

Congenital cardiac diseases in dogs: a retrospective analysis

In a time period of 6 years, 158 congenital cardiac defects were diagnosed in 146 dogs at the Clinic for Small Animal Medicine University of Zurich. In respect to all dogs with cardiac disease, these were 23.5% of the cases. Most common defects were subaortic stenosis (SAS, 31.5%), pulmonic stenosis (PS, 23.3%), ventricular septal defect (VSD, 14.4%), patent ductus arteriosus (PDA, 13.7%) and tricuspid dysplasia (TD, 7.5%). Complex defects were found in 8.2% of the dogs. Although single dogs per breed were affected by various defects, some breed-related tendencies could be observed. We found PS more numerously in boxers and Jack Russell Terriers whereas SAS, VSD and TD were also found in breeds reported to be predisposed. Congenital cardiac defects are an important clinical entity, and knowledge of prevalence is helpful when considering the differential diagnosis and for making a tentative diagnosis in an individual case.     

奥比沙星在兔体内的药物动力学研究

应用反相高效液相色谱法（RP—HPLC）研究奥比沙星在健康家兔体内的药物动力学规律。家兔以10mg/kg的单剂量肌肉注射奥比沙星,取给药后不同时间的血浆,用高效液相色谱仪测定血浆中奥比沙星的质量浓度,MCPKP药物动力学软件程序处理血浆药物浓度与时间数据。房室模型分析表明,免肌注给药的药时数据适合吸收二室开放模型：吸收和消除半衰期（T1／2Ka,T1/2β）分别为0．2669h和7．1546h;达峰时间（Tmax）为0．563h;峰浓度（Cmax）为4．8717μg／mL;药时曲线下面积（AUC）为18．4535mg／L·h。奥比沙星在家免体内的主要药动学特征为：吸收迅速,分布快,消除较缓慢,达峰时间短,峰浓度高,药时曲线下面积大。