Four dogs were given 5 mg/kg body weight enrofloxacin intravenously (i.v.) and orally (p.o.) in a cross-over study. Plasma concentrations of the active ingredient enrofloxacin and its main metabolite ciprofloxacin were determined by a reversed phase liquid chromatographic method. Pharmacokinetic parameters of both substances were calculated by use of statistical moments and were compared to those of enrofloxacin described in the veterinary literature. Mean enrofloxacin t1/2 lambda z was 2.4 h, mean Cls was 27.1 ml/min.kg, and mean Vss was 7.0 l/kg. After i.v. and p.o. administration, concentrations of ciprofloxacin exceeding minimal inhibitory concentrations of several microorganisms were reached (Cmax = 0.2 microgram/ml, tmax = 2.2 h after intravenous administration; Cmax = 0.2 microgram/ml, tmax = 3.6 h after oral administration). A considerable part of the antimicrobial activity is due to ciprofloxacin, the main metabolite of enrofloxacin.
Substantial changes occur in skeletal metabolism during lactation. These dynamic changes are monitored with biochemical bone markers. The goal of the present study was to follow these changes in lactating cows and to investigate whether cows with a higher milk yield have a higher mobilization rate of calcium from bone. Hydroxyproline, deoxypyridinoline, pyridinoline, and the carboxyterminal telopeptide of type I collagen (ICTP) were chosen as markers for bone resorption, whereas osteocalcin was used as a bone formation marker. Urine and blood samples were collected from cows with a mean standard milk yield of 4900 and 6500 kg, respectively, 14 d before, and 14 d, 1 mo, 1.5 mo, and monthly after parturition. Urinary hydroxyproline, deoxypyridinoline, and pyridinoline concentrations increased with time, but no differences between the two groups were evident. Concentrations of 1,25-dihydroxy vitamin D and ICTP of the two groups showed an increase 14 d after parturition. Furthermore, using multivariate regression models with age and milk yield as covariates, ICTP concentrations were higher in the group with a higher milk yield. In contrast, osteocalcin concentrations decreased 14 d after parturition and returned to prepartum values 1 mo after parturition. The increase of ICTP concentrations in both groups indicates that bone was substantially resorbed. At the same time, probably less Ca was embedded in bone, as indicated by the decrease of the osteocalcin concentrations. In conclusion, cows showed increased bone resorption around parturition, and cows with higher milk yield mobilize calcium more actively from bone than cows with lower milk yield.
Summary
Six pregnant sows were treated in early pregnancy, late pregnancy and during lactation. Marbofloxacin was administered (2mg/kg body weight) intravenously and orally. The active drug concentration in the plasma was quantitated by use of high performance liquid chromatography (HPLC). Pharmacokinetic parameters were calculated by use of statistical moments. In lactating animals, the concentrations in milk were also determined by HPLC. Mean elimination half‐life of the drug after oral administration was significantly shorter in lactating sows (5.74 h) than that of the early pregnancy group (10.09 h). Total body clearance was highest in the lactating sows (3.27 ml/minute · kg body weight). The volume of distribution was large in all physiological states studied indicating good tissue penetration. Bioavailability was about 80% in pregnant and lactating sows. Antimicrobial secretion in milk contributed greatly to marbofloxacin elimination. These results indicate an important influence of lactation on marbofloxacin pharmacokinetics in sows. Therefore, in such cases, marbofloxacin dose should be increased during lactation.
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