Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs

Brown, S.A., Jacobson, J.D., Hartsfield, S.M. Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs. J. vet. Pharmacol. Therap. 16 , 419–425. Midazolam, a water-soluble benzodiazepine tranquilizer, has been considered by some veterinary anaesthesiologists to be suitable as a combination anaesthetic agent when administered concurrently with ketamine because of its water solubility and miscibility with ketamine. However, the pharmacokinetics of midazolam have not been extensively described in the dog. Twelve clinically healthy mixed breed dogs (22.2–33.4 kg) were divided into two groups at random and were administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) either as an intravenous bolus over 30 s (group 1) or as an i.v. infusion in 0.9% NaCl (2 ml/kg) over 15 min. Blood samples were obtained immediately before the drugs were injected and periodically for 6 h afterwards. Serum concentrations were determined using gas chromatography with electron-capture detection. Serum concentrations were best described using a two-compartment open model and indicated a t_½α of 1.8 min and t_½β.p of 27.8 min after i.v. bolus, and t_½α f 1–35 min and t_½β of 31.6 min after i.v. infusion. The calculated pharmacokinetic coefficient B was significantly smaller after i.v. infusion (429 ± 244 ng/ml) than after i.v. bolus (888 ± 130 ng/ml, P = 0.004). Furthermore, AUC was significantly smaller after i.v. infusion (29 800 ±6120 ng/h/ml) than after i.v. bolus (42 500 ± 8460 ng/h/ml, P < 0.05), resulting in a larger Cl_B after i.v. infusion (17.4 ± 4.00 ml/min/kg than after i.v. bolus (12.1 ± 2.24 ml/min/kg, P < 0.05). No other pharmacokinetic value was significantly affected by rate of intravenous administration.     

Lack of effect of recombinant bovine interferon alpha I1 in the treatment of experimentally-induced bovine warts.

Fifteen four-month old calves were inoculated, on five scarified sites on each side of the neck, with a suspension of ground wart tissue from a steer naturally infected with bovine papilloma virus 1. Warts started to appear about one month postinfection and were measurable in ten calves two months postinfection, when the trial started. After stratification on the size of the warts, all fifteen calves were allocated randomly to one of the following treatment groups: twice weekly intramuscular injections of 5 mg recombinant bovine interferon alpha I1 (rBoIFN alpha I1), weekly injection of 5 mg of rBoIFN alpha I1 or placebo, for three weeks. The biggest wart on each calf at the beginning of the trial was measured and photographs of all warts were taken weekly for five weeks. An analysis of covariance on the log of the volumes of warts during the five weeks of the trial showed a significant difference between groups (p = 0.026). Warts in treated groups tended to grow faster than in the placebo group.     

The disposition of suxibuzone in the horse

A high performance liquid chromatographic method is described to determine the anti-inflammatory drug suxibuzone (SXB) and its major metabolites phenylbutazone (PBZ) and oxyphenbutazone (OPBZ) in equine plasma and urine. When suxibuzone (6 mg/kg) was administered intravenously (i.v.) or orally (p.o.) no parent drug was detected in plasma or in urine. The disposition of the metabolite PBZ (i.v.) could be described by a 2 compartment model with a P half-life varying from 7.40 to 8.35 h. Due to severe side effects the use of i.v. suxibuzone should not be encouraged in the horse. PBZ and OPBZ were detected in plasma and urine after p.o. SXB administration. Peak plasma PBZ concentrations (8.8 ± 3.0 μg/ml) occurred 6 h after oral dosing and the terminal exponential constant was 0.11 ± 0.01 h^-1. Phenylbutazone and oxyphenbutazone were detectable in urine (> 1 μg/ml) for at least 36 h, after p.o. administration.
SXB was not hydrolyzed in vitro by horse plasma. Equine liver homogenates however appeared to have a very high capacity for hydrolysing SXB, indicating that first-pass effect could be responsible for the rapid disappearance of this NSAID in the horse.     

An Epidemiologic and Economic Study of Respiratory Diseases in Two Conventional Danish Swine Herds. I: Prevalence of Respiratory Lesions at Slaughter and Their Effects on Growth

A total of 578 slaughter pigs from 2 Danish conventional farrow-to-finish operations (Herds A and B) were followed from an age of 14 days to slaughter. Pigs were weighed at 3 weeks intervals and at slaughter and an extended post mortem examination of the plucks was done. Comparison of growth rates in pigs with and without specific types of lesions by the t-test and those with multiple lesions with regression models demonstrated that Mycoplasma-like pneumonia, complicated pneumonia, anterio-ventral pleuritis, fissures and atrophic rhinitis significantly reduced mean daily gain and increased the time required to reach slaughter weight. The total impact of the lesions in Herd A was an estimated reduction in mean daily gain of 27 grams and a 2 day increase in the interval from 14 days of age until slaughter (MDG14). Decreases in MDG14 in Herd B were more substantial, 98 grams and 16.7 days. Reductions in mean daily gains during the interval from the fourth weighing until slaughter were 31 grams in Herd A and 137 grams in Herd B. Chronic dorso-caudal and parietal pleuritis, without other lesions present, had no significant adverse effects on growth rates in either herd. Interactions between lesions did not significantly alter the estimates. The R² values obtained for the regression models showed that the presence, absence or extent of lesions at slaughter explained only 13-27% of the variations in growth rates in the 2 herds.     

Quantitative analysis of canine plasma lipoproteins

A combined ultracentrifugationl/precipitation method for the measurement of lipoprotein cholesterol concentrations was developed and validated for use with canine plasma. Very low density lipoproteins (VLDL) were isolated by flotation ultracentrifugation and low density lipoproteins (LDL) separated from high density lipoproteins (HDL) by precipitation with heparin-manganese chloride. Effective separation of these classes was confirmed by agarose gel electrophoresis of native lipoproteins and by sodium dodecyl sulphate polyacrylamide gel electrophoresis of their apolipoprotein distributions. There was trace contamination of the LDL precipitate with HDL, but this represented less than 4 and 9 per cent of the total plasma HDL in normo- and hypercholesterolaemic dogs, respectively. The intra-assay and interassay coefficients of variation for LDL- and HDL-cholesterol concentrations were between 3·3 and 6·9 per cent, and 7·2 and 9·0 per cent, respectively, for plasma cholesterol concentrations between 2·67 and 8·14 mmoll/litre. The intra-assay coefficient of variation for VLDL-cholesterol was 53·8 and 18·4 per cent at plasma cholesterol concentrations of 2·67 and 8·14 mmol/litre, respectively. The interassay coefficient of variation for VLDL was 22·5 per cent. Storage of plasma at -20°C for between two and eight weeks did not affect VLDL-cholesterol concentrations, but led to an increase in LDL-cholesterol and a decrease in HDL-cholesterol concentrations of approximately 10 per cent. The method described is appropriate for the measurement of lipoprotein concentrations in plasma from normo- and hypercholesterolaemic dogs, but samples should not be subjected to prolonged storage before analysis.     

Radiographic interpretation of normal skeletal variations and pseudolesions in the equine foot.

Effective radiographic interpretation requires a veterinarian who is knowledgeable of equine limb anatomy and the various principles that affect the resulting image. The normal and its variations must be recognized and understood before the abnormal can be confidently identified as pathologic. Proper patient positioning and sound radiographic technique are mandatory if reliable diagnostic radiographs are to be produced. This review emphasizes equine foot radiographic variations of normal and pseudolesions that occur with commonly used radiographic views performed in equine practice.     

Relationships between clinical and pathological signs of disease in calves infected with Mannheimia (Pasteurella) haemolytica type A1.

Respiratory disease was induced in 16 calves, and the terminal clinical signs of disease and postmortem pathological observations were recorded. By Spearman's correlation coefficient, the respiratory rate, rectal temperature and clinical scores of the calves were significantly correlated with the extent of lung consolidation. The respiratory rate was the clinical sign most consistently correlated with the other clinical and pathological signs of respiratory disease.     

Nitrogen uptake by ryegrass from organic wastes applied to a sandy loam soil

Sandy‐textured Mediterranean soils are invariably depleted in organic matter and supply only small amounts of N to crops. To compensate for these deficiencies, we tested the N supply from six organic wastes applied to a Cambic Arenosol in pots growing ryegrass. The results showed that the behaviour of the wastes in supplying N to a ryegrass crop grown in this soil can be predicted by observing their performance in laboratory aerobic incubations. The N made available during these incubations fitted well to a one‐pool kinetic model.