Abstract. In safety pharmacology studies, the effects on the QT interval of electrocardiograms are routinely assessed using a telemetry system in cynomolgus monkeys. However, there is a lack of integrated databases concerning in vivo QT assays in conscious monkeys. As part of QT Interval Prolongation: Project for Database Construction (QT PRODACT), the present study examined 10 positive compounds with the potential to prolong the QT interval and 6 negative compounds considered to have no such effect on humans. The experiments were conducted at 7 facilities in accordance with a standard protocol established by QT PRODACT. The vehicle or 3 doses of each test compound were administered orally to male cynomolgus monkeys (n = 3 -4), and telemetry signals were recorded for 24 h. None of the negative compounds prolonged the corrected QT using Bazett's formula (QTcB) interval. On the other hand, almost all of the positive compounds prolonged the QTcB interval, but haloperidol, terfenadine, and thioridazine did not. The failure to detect the QTcB interval prolongation appeared to be attributable for the differences in metabolism between species and / or disagreement with Bazett's formula for tachycardia. In the cynomolgus monkeys, astemizole induced Torsade de Pointes and cisapride caused tachyarrhythmia at lower plasma concentrations than those observed in humans and dogs. These results suggest that in vivo QT assays in conscious monkeys represent a useful model for assessing the risks of drug-induced QT interval prolongation. Supplementary material (Appendix): available only at http://dx

Elobixibat induces bowel movements faster than sennoside through a different mechanism. Elobixibat locally inhibits IBAT in the ileal lumen, leading to elevated fecal BAs in the colon and induced mild GMCs during defecation.

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The general pharmacological effects of the hexapeptide KP-102 (D-alanyl-3-(2-naphthyl)-D-alanyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide dihydrochloride, growth hormone-releasing peptide-2, GHRP-2, pralmorelin, CAS 158861-67-7), which potently promotes growth hormone (GH) release by acting at both hypothalamic and pituitary sites, were evaluated in various animal experimental models. The administration of KP-102 showed no obvious effect at a pharmacological dose on the central nervous system. KP-102 had no significant effect on the autonomic nervous system and smooth muscle except a slight and transient increase in spontaneous motility of isolated rabbit ileum and contraction of isolated guinea pig ileum at high doses. There was negligible effect on the respiratory and cardiovascular systems, digestive system, renal function and blood system after KP-102 treatment. These results suggest that KP-102 has no serious general pharmacological effects at dose levels showing GH-releasing activity in the experimental animals. Therefore, it is concluded that KP-102 will be a useful drug for the diagnosis of serious GH deficiency and for treatment of short stature.

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