A pharmacokinetic study to evaluate the piglet as a model for caffeine and theophylline disposition was undertaken in 28 animals who received a 10.0-mg/kg intravenous dose of either methylxanthine, followed by multiple blood sampling over a 24-hour period. Theophylline and caffeine concentrations were quantitated from serum using a microanalytical HPLC technique (coefficient of variability <7% at 0.1-100 mg/1). The influence of postnatal development on drug disposition was examined by dividing the experimental animals into three age groups (newborn, 2 days; perinatal, 4-5 days; infants or young, 15-22 days). Pharmacokinetic parameters were calculated from nonlinear curve fitting of serum concentration vs time data. On the basis of the terminal elimination rate constant (λz) and total clearance (CL) for both theophylline and caffeine, differences were found among the age groups. The apparent volume of distribution (V(z)) for both methyl- xanthines was not found to be different when compared between age groups. Covariance determinations between age and pharmacokinetic parameters revealed linear correlations for V(z) of caffeine and CL for both theophylline and caffeine. In all piglets receiving theophylline, no caffeine was detected in serum during a 24 hr period. Theophylline, however, was detected (0.4 ± 0.2 mg/1 at 11.5 hr) in the four oldest piglets who received caffeine. Similarities between pharmacokinetic parameters for caffeine and theophylline reported for human neonates were found only for newborn piglets. Furthermore, the biotransformation of theophylline to caffeine reported for human neonates was not observed in neonatal piglets.
The ability of soybean oil lipid emulsions to affect essential fatty acid deficiency (EFAD) and plasma fatty acid distribution was studied in neonatal pigs. The test animals were maintained on a fat-free diet prior to administration of lipid emulsion. Plasma and red blood cell (RBC) membrane levels of essential [linoleic (C-18:2 omega 6) and arachidonic (C-20:4 omega 6)] and nonessential [palmitic (C-16, palmitoleic (C-16:1 omega 7), stearic (C-18), and oleic (C-18:1 omega 9)] fatty acids and the triene:tetraene ratio [5,8,11-eicosatrienoic acid (C-20:3 omega 9):arachidonic acid (C-20:4 omega 6)] were monitored to ascertain the establishment of EFAD and its correction. Nonessential fatty acids were studied, as these components of lipid therapy have received little attention. Results indicate that soybean oil emulsions are effective in reversing fatty acid profiles found in EFAD, and both essential and nonessential fatty acids are under strict metabolic control.
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