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.
Intracellular glycolytic regulating enzyme activities, pyruvate kinase (PK) and phosphofructokinase (PFK), adenylate kinase (AK), energy charge (Ech), free amino acids (ICAA), and protein synthesis (PS) were measured in polymorphonuclear leukocytes--used as a cell model--in 62 adults and 12 children with chronic renal failure, and 66 normal adults and 21 children as comparison controls. In normal subjects, children had significantly lower enzyme activities and cell amino acid levels but similar Ech and higher PS than adults. ICAA concentrations were significantly higher than plasma amino acid concentrations (PAA) in both groups, and the PAA were not correlated with, nor indicative of, the ICAA concentrations. The variance (R2) in PS could be largely accounted for by a combination ("set") of six ICAA, as determined by multivariate analysis. The sets differed in children vs adults, suggesting that different proteins were being synthesized. In the uremic patients, reduced PF, PFK, Ech, most ICAAs and PS were indicative of cellular malnutrition. For the uremic adults, the abnormalities in cell metabolism were modified by therapy--nondialyzed uremics being worst, CAPD patients best and approximately normal, and hemodialyzed intermediate. The uremic CAPD children had reduced, PK, PFK, AK, most ICAA, and PS. Ech was increased. Cellular malnutrition in children with chronic renal failure may contribute to their poor growth.
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