A pharmacokinetic study of peritoneal absorption of glucose and alanine in rats: nutritional implications.

BACKGROUND: The aim of this work was to study the serum bioavailability of glucose and alanine after bolus injection into the peritoneal cavity in Wistar rats and to determine the influence of their metabolism on the rate of absorption of these nutrients. METHODS: A group of animals (n = 14) was infused intraperitioneally (i.p.) or i.v. with 2 microCi of nonmetabolizable L-[1-14C] glucose diluted in 5 mL of 5% D-glucose/250 g body wt, after which plasma radioactivity was determined. A second group of animals (n = 14) received, either i.p. or i.v., 3 microCi of nonmetabolizable D-[U-14C] alanine diluted in 2 mL of an iso-os-molar L-amino acid solution/250 g body wt, after which both plasma radioactivity and L-alanine concentration were determined. The constants of absorption from peritoneal cavity (Ka) and elimination from plasma (Ke) and the serum absolute bioavailability (BA(a)) after 8 h were calculated assuming a bicompartment pharmacokinetic model. RESULTS: L-glucose: Ka = 3.05 +/- 0.97 h-1; Ke = 0.40 +/- 0.12 h-1; BA(a) = 94% +/- 4%. D-alanine: Ka = 1.08 +/- 0.40 h-1; Ke = 0.11 +/- 0.06 h-1; BAa = 90% +/- 11%. L-alanine: Ka = 1.75 +/- 0.273 h-1; Ke = 0.02 +/- 0.01 h-1; BA(a) = 99% +/- 1%. No hyperglycemia, hypoglycemia, or glycosuria appeared in any case. CONCLUSIONS: The absorption rate from peritoneal cavity is nearly 10-fold higher than the elimination rate from plasma for the three substrates. Eight hours after i.p. injection an absolute bioavailability almost as high as after i.v. injection (i.e., close to 100%) was achieved. The metabolism of the nutrients seems to help the peritoneal absorption, as L-alanine is better absorbed then D-alanine. These results show that upon i.p. injection the studied nutrients are almost completely absorbed in a short period of time without hyperglycemia or neoglucogenesis and so suggest that their administration may be a feasible approach to feeding patients receiving peritoneal dialysis. This model could be applied to other compounds, such as peptides and disaccharides.

Long term peritoneal nutrition in dogs, both normal and after intestinal resection.

We carried out total and prolonged peritoneal nutrition (PN) in a group of healthy dogs and in another group that had previously undergone an 80% resection of the small intestine. A third group of animals underwent the same operation but did not receive intraperitoneal nutrition, as they formed the control group. A nutritive mixture was used, composed of glucose fat emulsion, aminoacids, ions, trace elements, insulin and vitamins. The caloric rate was 45 kcal/kg/day. Peritoneal nutrition lasted 30 days. Periodical clinical controls were made for biochemical, hematological, microbiological and histopathological analyses. We found two episodes of peritonitis out of a total of 19 dogs subjected to PN. Hyper- and hypoglycemia occurred in the animals with PN and that had not undergone intestinal resection there were also increases in triglyceride, free fatty acid and cholesterol levels as well as a reduction of albumin. We observed a greater decrease in albumin and urea nitrogen and a greater weight loss in the animals underwent intestinal resection. The quantity absorbed was greater than 95% of the volume infused over the four week period. In all the animals subjected to PN we found hyperplasia and phagocytic phenomena in the peritoneal mesothelium cells after 30 days of peritoneal nutrition, symptoms which disappeared one month after this kind of nutrition was stopped.

Long-term peritoneal nutrition in dogs: metabolic and histopathologic results.

In order to test the use of the peritoneal cavity in prolonged nutrition, seven dogs were fed for 22 days via peritoneal catheter. The nutritive preparations were composed of 10% crystalline amino acids, 20% fat emulsion, 40% glucose, trace elements, Na+, K+, insulin and a multivitamin compound. The caloric rate was 45kcal/kg/24h plus 0.5g/kg/24h of amino acids. These animals were compared to another group of six dogs, which were catheterized and infused with a 3% saline solution in addition to an oral intake of 45kcal/kg/24h. Both groups had free use of water. There was a case of slight peritonitis in one dog on peritoneal nutrition but no deaths and no weight changes occurred throughout the experiment. Increases in serum levels of TG, FFA and cholesterol were observed in the animals treated with peritoneal nutrition as well as a decrease in albumin serum levels. Peritoneal hyperplasia and phagocytosis were noted in the animals on peritoneal nutrition but no damage was recorded in other organs.

Biochemical and histopathological findings after a long-term intraperitoneal fat infusion. An experimental study in rats.

The object of this work was to see the possible side effects that a long-term intraperitoneal (IP) fat infusion would have. We used 56 female Wistar rats weighing 250 g, divided into a control group (CG) of eight and three groups of 16 in each one. These three groups were administered a 20% Intralipid infusion in a daily amount of 4 g/kg over 5, 10, and 15 days, respectively (groups I, II, and III) intraperitoneally. Twenty-four hr after the last infusion the animals were anesthetized and after having drawn 3 ml of blood, 5% glutaraldehyde (GTH) was instilled in situ and optical and electron microscopic specimens were taken of the lung, liver, right diaphragm, and parietal peritoneum. The results show a decrease in triglyceride (TG) rate 24 hr after the last infusion in each group, but blood glucose, cholesterol, bilirubin, glucose oxidase test (GOT), glutamic pyruvic transaminase (GPT), nor other serum parameters varied. No alterations were noticed in the lung or liver under optical or electron microscopes in the groups than had under gone treatment, except for an increase in circulating macrophages with fat in the lung. In the diaphragm we observed hyperplasia in the serous layer of the peritoneum and an increase in fat in the lymphatic channels of the right diaphragm. The possibility of using IP infusions in order to study parenteral nutrition solutions was put forward as well as their possible clinical use in alternative nutrition techniques on both a short-term and long-term basis.