Effect of food on gastrointestinal transit of liquids in cynomolgus monkeys

Abstract

We investigated the gastrointestinal transit of liquids, as well as various gastric pH profiles, in fed cynomolgus monkeys. Twelve grams of a biscuit-type solid food were provided 1 h before the test. The acetaminophen method was used to determine the gastric half-emptying time (t(50%)), which provided an estimate of the gastric emptying rate. The gastric emptying rate of liquids was significantly reduced after food intake in monkeys. The mean t(50%) value was 143.5 min and comparable to that of humans after eating. However, there was a large variability in the t(50%) between individual animals as shown by the coefficient of variance of approximately 80%. Next, the median oro-caecal transit time in fed monkeys was determined to be 1.8 h, using the sulfasalazine-sulfapyridine method. There was no significant difference in oro-caecal transit time between unfed and fed monkeys; thus, food intake has no significant effect on the oro-caecal transit time of liquids in either monkeys or humans. However, the oro-caecal transit time in humans is about 2 h longer than that in monkeys. Our experiments using several different foods suggested that the typical human gastric pH profile could not be simulated in fed monkeys.

Effect of Food Status on the Gastrointestinal Transit of Amphotericin B-Containing Solid Lipid Nanoparticles in Rats

“…A number of studies on pellets or suspensions have estimated cecal arrival time as the time for the initial detection of SP in plasma (20)(21)(22)26). In the present study, T 10S was used to estimate CAT of the AmB SLNs instead of the time for the first appearance of SP in plasma which with most certainty is a result of SSZ released from the SLN as solution and arriving at the cecum ahead of the SLNs.…”

“…In the present paper, we describe the pharmacokinetics of AmB as a consequence of food status and the GI transit of AmBcontaining SLNs using an indirect estimation method (20)(21)(22). Paracetamol (PAR) was used to estimate the GTT of the SLNs based on the rate of its appearance in the blood following oral administration of PAR-containing SLNs (23) similarly formulated as the AmB and sharing identical physical characteristics (5).…”

“…PAR and SP have been used as marker drugs to estimate the gastric emptying (GE) and orocecal transit times of pelletfilled capsules in humans (20,26) and liquids in monkeys (21,22), as well as in our previous pilot study (5). These marker drugs provide a cheaper, safer, and more appropriate alternative to the use of gamma scintigraphy for evaluating GI transit of pharmaceutical formulations in experimental animals like rats.…”

Pharmacodynamic and Pharmacokinetic Evaluation of CS-526 in Cynomolgus Monkeys

“…Although the data from non-human primates would be useful for the prediction of clinical study results due to their phylogenetic similarities, the background knowledge of gastric acid secretion in primates is still lacking. There are only a few reports regarding the physiologic state of gastric acid secretion [22][23][24][25][26][27] and less than 10 reports of pharmacodynamic studies. [28][29][30][31][32][33][34] In these pharmacodynamic studies, gastric juice or infused wash solution was collected from acute gastric fistulae in anesthetized animals or nasogastric tubes in monkey chair restrained animals, respectively.…”

“…21) There are a great number of reports in which the effects of agents on gastric acid secretion are evaluated in rats and dogs. However, in terms of monkeys, there are only a few reports regarding gastric acid status [22][23][24][25][26][27] and less than 10 reports of pharmacodynamic studies. [28][29][30][31][32][33][34] However, we think it would be meaningful to obtain data from non-human primates because of their phylogenetic similarities with human beings.…”