Search

Background: Upregulation of oligopeptide transport activity by dietary protein, certain dipeptides and amino acids has been reported in the rat intestine and a human intestinal cell line. Objective: In this study, the pharmacokinetics of cefdinir were investigated afterl-phenylalanine supplementation and a high-protein diet (HPD) in humans to explore changes in the activities of intestinal and renal oligopeptide transporters. Methods: A normal-protein diet (NPD, 73·2 ± 2·6 g/day), NPD + l-phenylalanine (7·5 g/day), or HPD (141·3 ± 3·7 g/day) was given to six male healthy volunteers for 12 days followed by a single dose of cefdinir after an overnight fast in a randomized three-way crossover study with a 22-day washout. Blood and urine were collected over a 12-h period after administration of cefdinir. Concentrations of cefdinir in plasma and/or urine were measured by high-performance liquid chromatography. Results: Plasma concentrations and urinary excretion of the drug did not change throughout the study. Physiological variables and laboratory values did not reveal any differences between the three periods except for serum and urinary nitrogen levels and serum triglyceride. Discussion: A reason for the unchanged pharmacokinetics of cefdinir may be due to lower doses ofl-phenylalanine and protein in humans than in animals when converting animal effective doses to humans. Conclusion: In humans,l-phenylalanine supplementation and HPD do not seem to upregulate intestinal and renal oligopeptide transport in the ranges of duration and dose examined. [ABSTRACT FROM AUTHOR]

Background: MKC-733, a 5-HT3 receptor partial agonist, is a novel enteroprokinetic compound. Objective: The aim of this study was to explore the effects of MKC-733 on bowel motility and symptoms in a small group of subjects with constipation. Tolerability was also examined. Methods: The study was conducted in a single-blind and dose-escalation manner on 14 male and female subjects with constipation aged 22–67 years. After a 1 week run-in period, subjects were treated with placebo (b.i.d.) for 1 week, and 0·2 and 0·5 mg of MKC-733 (b.i.d.) for 2 weeks sequentially. Geometric mean and per cent elimination of surrogate markers of bowel motility were measured by a radio-opaque marker technique at the end of each treatment period. They were analysed on the whole group and subgroups with low ( n = 6) and high ( n = 8) bowel motility based upon the geometric mean value after placebo treatment. Subjects kept diaries of their bowel habits and gastrointestinal symptoms. Results: Percent elimination increased after treatment with 0·5 mg MKC-733 compared with placebo treatment in the whole group (70·4 ± 33·5% vs. 47·1 ± 36·6%, mean ± SD, P < 0·05). In the low bowel motility group, both geometric mean and percent elimination increased after treatment with 0·5 mg MKC-733 compared with placebo (7·1 ± 0·9 vs. 5·9 ± 0·5, P < 0·05; 60·0 ± 35·8% vs. 13·3 ± 19·4%, P < 0·05). Stool frequency increased after the first-week treatment with MKC-733 compared with placebo ( P < 0·05). Numbers of sensation of incomplete evacuation and gastrointestinal symptoms decreased to half and less after the treatment with MKC-733. No serious adverse effect was noted. Conclusion: Multiple doses of 0·5 mg MKC-733 improve bowel motility, which was clearly demonstrated in the subjects with decreased bowel motility. MKC-733 at the doses studied might be effective in increasing stool frequency and reduce gastrointestinal symptoms related to constipation. MKC-733 was well tolerated. Further studies will be needed to clarify efficacy and safety of MKC-733 on a larger population. [ABSTRACT FROM AUTHOR]