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  • Author or Editor: Valérie Laroute x
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Abstract

Objective—To assess the effects of moderate exercise on plasma creatine kinase (CK) pharmacokinetics and to estimate exercise-induced muscle damage in dogs.

Animals—6 untrained adult Beagles.

Procedure—The study was divided into 3 phases. In phase 1, dogs ran for 1 hour at a speed of 9 km/h, and samples were used to determine the area under the plasma CK activity versus time curve (AUC) induced by exercise. In phases 2 and 3, pharmacokinetics of CK were calculated in dogs during exercise and at rest, respectively. Values for AUC and plasma clearance (Cl) were used to estimate muscle damage.

Results—At rest, values for Cl, steady-state volume of distribution (Vdss), and mean retention time (MRT) were 0.32 ± 0.02 ml/kg of body weight/min, 57 ± 17.3 ml/kg, and 3.0 ± 0.57 h, respectively. During exercise, Cl decreased significantly (0.26 ± 0.03 ml/kg/min), MRT increased significantly, (4.4 ± 0.97 h), and Vdss remained unchanged. Peak of plasma CK activity (151 ± 58.8 U/L) was observed 3 hours after completion of exercise. Estimated equivalent amount of muscle corresponding to the quantity of CK released was 41 ± 29.3 mg/kg.

Conclusion and Clinical Relevance—These results revealed that exercise had a minor effect on CK disposition and that the equivalent amount of muscle damaged by moderate exercise was negligible. This study illustrates the relevance for use of the minimally invasive and quantitative pharmacokinetic approach when estimating muscle damage. (Am J Vet Res 2001;62:1375–1380)

Full access
in American Journal of Veterinary Research

Abstract

Objectives—To investigate and validate noninvasive methods for the quantitative evaluation of postinjection muscle damage.

Animals—5 adult sheep.

Procedures—Muscle lesions were induced twice in the lumbar region of the longissimus dorsi muscles (2 sides) by IM administration of a 20% formulation of long-acting oxytetracycline (20 mg/kg of body weight). Clinical signs and local cutaneous temperature above the injection site were recorded. Muscle lesions were quantitatively evaluated by ultrasonography and by use of pharmacokinetic analysis of plasma creatine kinase activity, and both were compared with a comprehensive planimetric computer-assisted analysis of the injection sites after euthanasia.

Results—Transient cutaneous hypothermia (temperature change, –3.9 ± 0.62 C) and subsequent persistent hyperthermia (3.1 ± 1.35 C) were observed after the administrations. Despite coefficient of variation < 10% for precision of ultrasonographic measurement of normal muscle, measurements of the lesions, with coefficient of variation > 60% for precision, were systematically underestimated. Quantitative evaluation of muscle damage by use of pharmacokinetic analysis of creatine kinase (12.1 ± 4.96 g) was in agreement with results of macroscopic planimetric evaluation (10.8 ± 3.64 g).

Conclusions and Clinical Relevance—Ultrasonography cannot be used for quantitative assessment of postinjection muscle damage. Pharmacokinetic analysis of creatine kinase provides an accurate quantitative evaluation of macroscopic muscle damage after IM administration of drugs. (Am J Vet Res 2001;62:1698–1705)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine pharmacokinetic parameters for meloxicam, a nonsteroidal anti-inflammatory drug, in horses.

Animals—8 healthy horses.

Procedure—In the first phase of the study, horses were administered meloxicam once in accordance with a 2 × 2 crossover design (IV or PO drug administration; horses fed or not fed). The second phase used a multiple-dose regimen (daily oral administration of meloxicam for 14 days), with meloxicam administered at the recommended dosage (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of validated methods with a limit of quantification of 10 ng/mL for plasma and 20 ng/mL for urine.

Results—Plasma clearance was low (mean ± SD; 34 ± 0.5 mL/kg/h), steady-state volume of distribution was limited (0.12 ± 0.018 L/kg), and terminal half-life was 8.54 ± 3.02 hours. After oral administration, bioavailability was nearly total regardless of feeding status (98 ± 12% in fed horses and 85 ± 19% in nonfed horses). During once-daily administration for 14 days, we did not detect drug accumulation in the plasma. Meloxicam was eliminated via the urine with a urine-to-plasma concentration that ranged from 13 to 18. Concentrations were detected for a relatively short period (3 days) after administration of the final daily dose.

Conclusions and Clinical Relevance—Results of this study support once-daily administration of meloxicam regardless of the feeding status of a horse and suggest a period of at least 3 days before urine concentrations of meloxicam reach concentrations that could be used in drug control programs. (Am J Vet Res 2004;65:1542–1547)

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in American Journal of Veterinary Research

Abstract

Objective—To investigate the effects of preventive angiotensin converting enzyme inhibitor treatment with ramipril in dogs with progressively severe experimentally induced heart failure.

Animals—20 dogs.

Procedures—Dogs were randomly allocated to receive no treatment (control) or ramipril (0.125 mg/kg, PO, daily) for 7 weeks. Physical examination, repetitive catheterization of the right side of the heart, and echocardiography were performed before the study (day 0) and weekly for 7 weeks. Renal plasma flow (RPF) as determined by para-aminohippuric acid clearance and glomerular filtration rate (GFR) as determined by creatinine and iohexol clearances were measured on day 0 and at weeks 4 and 7.

Results—Overpacing induced a progressive increase in right atrial pressure (RAP) and pulmonary artery pressure, occluded (PAPO), with a decrease in systemic arterial pressure. There were progressive alterations of echocardiographic indices of diastolic and systolic ventricular function. The RPF and GFR decreased before cardiac output decreased, and filtration fraction increased. The logarithm of the urinary sodium–to–potassium concentration ratio (log10[Na+/K+]) decreased. Significant effects of ramipril included a delay in clinical signs of heart failure, a late decrease in RAP and PAPO, and increases in the sodium excretion fraction and log10(Na+/K+). There was a satisfactory agreement between the creatinine and iohexol clearance measurements.

Conclusions and Clinical Relevance—Results suggest that, in this rapid-evolving, dilated cardiomyopathy, activation of the renin-angiotensin system contributes to the pathophysiology of heart failure late in the disease and essentially by an activation of renal salt and water retention.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To measure florfenicol concentrations in ovine tear fluid after IM and SC administration and determine minimum inhibitory concentrations (MICs) of florfenicol against field isolates of Mycoplasma organisms potentially involved in infectious keratoconjunctivitis.

Animals—9 healthy adult Lacaune ewes.

Procedures—Animals received an IM and SC administration of florfenicol (20 mg/kg) in a 2-way crossover design. Samples of blood and tear fluid were collected before and for 24 hours after administration. Concentrations of florfenicol in plasma and tear fluid were measured via high-performance liquid chromatography. The MIC of florfenicol for various Mycoplasma strains cultured from sheep and goats was determined via an agar dilution method.

Results—Mean florfenicol concentration in tear fluid for the 24-hour period was significantly higher after IM administration (0.70 μg/mL) than after SC administration (0.22 μg/mL) and was maintained for a longer duration. The lacrimal fluid-to-plasma concentration ratio was not different between the 2 routes of administration, with mean values of 40.2% and 32.5% after IM and SC administration, respectively. The MIC for Mycoplasma agalactiae, Mycoplasma conjunctivae, and Mycoplasma mycoides isolates ranged from 0.5 to 8 μg of florfenicol/mL. Two strains of M agalactiae could be considered resistant to florfenicol.

Conclusions and Clinical Relevance—Florfenicol readily penetrated the preocular tear fluid of sheep after IM and SC administration. For both routes of administration, doses > 20 mg/kg would be necessary to achieve tear fluid concentrations of florfenicol greater than the MICs for most strains of Mycoplasma organisms.

Full access
in American Journal of Veterinary Research