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The plasma concentrations, tissue distribution and excretion of prostaglandin A1 (PGA1) and related metabolites have been determined in rats, following the intravenous injection of a single dose of PGA1-5,6-3H. Urinary and faecal excretion accounted for averages of 25 and 43%, of the administered dose of PGA1, respectively. Oxidative cleavage of the carboxyl side chain of PGA1 appeared to be a major metabolic pathway in the rat. PGA1-5,6-3H was deemed unsuitable for metabolism studies in man, in view of the significant loss of tritium label from the prostaglandin.

1. Circulating concentrations of glucose, propionate, lactate and pyruvate, and net exchange of these compounds across the liver and gut, were measured in lactating and non-lactating dairy cows (a) in the normal fed state, (b) before, during and after intravenous infusion of an aqueous solution of glucose, propionate or lactate (lactating cows only) in fed animals, and (c) before and during 6 days of food deprivation. 2. In the normal fed state, gut output of propionate, hepatic output of glucose and hepatic uptake of lactate were all higher in the lactating group. There was a net uptake of pyruvate across the liver in the lactating cows and a net output in the non-lactating cows. In the lactating cows there was a net uptake of lactate and pyruvate by the splanchnic bed (i.e. gut and liver combined). 3. In the lactating cows, the glucose and propionate infusions had the following effects: decrease in net hepatic uptake of lactate; a switch in pyruvate exchange across the liver from uptake to output; suppression of uptake of lactate and pyruvate by the splanchnic bed; increase in the magnitude of the liver (propionate uptake)/(glucose output) ratio. Lactate infusion did not affect hepatic propionate uptake. 4. Food deprivation increased hepatic extraction of lactate and pyruvate and decreased the liver (propionate uptake)/(glucose output) ratio in both groups. 5. It is concluded that mechanisms exist to ensure an inverse relationship between the availability to the cow of glucose or propionate and utilization by the splanchnic bed of endogenously derived lactate and pyruvate.

Thermodilatometric, dynamic thermomechanical, and light-microscopic analyses were done on the anterior and posterior regions of the rat knee menisci to correlate regional differences in morphology and extracellular matrix composition with regional mechanical behavior. Following the administration of a general anesthetic, menisci were excised from 12 young female Sprague-Dawley rats. During thermodilatometric and thermomechanical testing, tissue temperature was increased at a constant rate of 3.5 degrees C/min from 30 to 100 degrees C. Light microscopy revealed regional differences in cell density and proteoglycan content. The anterior horn was significantly heavier (greater than 87%) and thicker (greater than 60%) than the posterior region. During thermal analyses, both the anterior and posterior horns decreased in tissue thickness as the temperature increased from 30 to 73 degrees C. After 73 degrees C, however, the posterior horn expanded significantly, whereas the anterior remained in a comparatively contracted state. The rates of linear contraction and expansion of the posterior horn were seven times those of the anterior horn, and the stiffness of the anterior horn was significantly greater than the posterior horn.

The urinary metabolites of arbaprostil-3H in the male rat were profiled, isolated, and purified. Their structures were deduced by gas chromatography/mass spectrometry (GC/MS) studies after conversion to the methyl ester-methoxime-trimethylsilyl ether derivatives, aided by GC with simultaneous radioactivity monitoring. The identified metabolites accounted for over 91% of the urinary excretion products. beta-oxidation of the carboxy side-chain of arbaprostil to 15-methyl-tetranor PGE1 appeared to be the most significant metabolic pathway. Conversion to the dinor A and B derivatives and further beta-oxidation of these to the 15-methyl-tetranor A and B metabolites also appeared to occur. C-19-hydroxylated tetranor A and B derivatives of arbaprostil-3H were excreted in the urine. No conjugated urinary metabolites were evident.

A single dose of arbaprostil-11 beta-3H (4 micrograms/kg) was administered orally to male rats. A maximum plasma radioactivity concentration equivalent to 2.5 to 2.8 nanograms of the prostaglandin per ml was reached at 30 minutes and was maintained until 120 minutes after drug administration. The plasma drug disappearance half-life was 2.6 hours. These results along with data from tissue distribution studies suggested a rapid uptake of radiolabeled arbaprostil by the glandular stomach tissue followed by an apparent zero-order release of drug-related radioactivity from this tissue "reservoir" into the plasma. Drug-related radioactivity was excreted rapidly, with 96 to 99% of the urinary excretion and 82 to 97% of the fecal excretion being completed within 24 hours. A total of 49.6 +/- 3.5% of the orally administered dose was excreted in the urine and 46.7 +/- 3.9% in the feces. No radioactive residues were detected in the animals at the end of the 120 hour specimen collection period. The metabolic stability of the 11 beta-tritium label and the suitability of arbaprostil-3H for use in human studies was demonstrated.