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  • Author or Editor: J. Edmond Riviere x
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in Journal of the American Veterinary Medical Association

SUMMARY

Pharmacokinetic variables were calculated from time-concentration data obtained after iv (10 mg/kg of body weight; n = 9) and oral (12.5 mg/kg to group A [n = 3]; 25 mg/kg to group B [n = 3]; and 50 mg/kg to group C [n = 3] pigs) cyclosporine (formerly, cyclosporine A) administration. Resulting mean (± sd) pharmacokinetic variables were as follows: half life of distribution, 0.96 (± 0.7) hours; half life of elimination, 7.71 (± 2.6) hours; volume of distribution at steady state, 4.47 (± 2.22) L/ kg; volume of the central compartment, 1.71 (± 0.78) L/ kg; and systemic clearance, 8.95 (± 2.7) ml/kg/min. Oral bioavailability was: overall 57 (± 19) %; group A, 44 (± 11) %; group B, 78 (± 15) %; group C, 48 (± 6) %. Time to peak concentration was 3.55 (± 0.88) hours. During the 22 days of daily oral cyclosporine administration, blood 24-hour trough concentrations were: group A, 224.3 (± 78.4) ng/ml; group B, 640.7 (± 174.6) ng/ml; and group C, 2,344 (± 1,095) ng/ml. Lymphoblast transformation stimulation index was suppressed in all pigs except 1, which had a corresponding cyclosporine concentration of 92.4 ng/ml. Minimal, although statistically significant, decreases in serum albumin and magnesium concentrations and increases in serum creatinine and urea nitrogen concentrations were evident in pigs of some treatment groups. Histologic examination of necropsy specimens revealed mild hepatic necrosis (n = 1 pig), renal tubular dilatation (n = 5), and pulmonary inflammation (n = 2). Pigs given 25 and 50 mg of cyclosporine/kg failed to gain weight.

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in American Journal of Veterinary Research

SUMMARY

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.

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in American Journal of Veterinary Research

SUMMARY

The assessment of cutaneous microcirculation by laser-Doppler velocimetry (ldv) has been primarily limited to human studies. The purpose of this investigation was to establish normal values in various species and anatomic sites for blood flow, velocity, and volume as determined by ldv. Microcirculation was measured with a laser-Doppler velocimeter in 54 animals, 6 healthy animals from each of 9 species. The standard sites used were the buttocks, convex surface of the ear, metacarpal pad, humeroscapular junction, thoracolumbar junction, ventral portion of the abdomen, dorsal metacarpus (hooved animals), and ventral surface of the tail (horse). Significant differences in blood flow, velocity, and volume were measured between species and sites within species. The ventral portion of the abdomen consistently had the highest relative blood flow across all species except the monkey. Measurements in the canine metacarpal pad had a high sd, possibly indicating the stratum corneum and epidermis to be too thick for ldv. Our findings provide baseline data in several species, with application of ldv in comparative dermatologic research.

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in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association