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CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide.
- Tanja Busk Bidstrup, I. Bjørnsdottir, U. Sidelmann, M. Thomsen, K. Hansen
- Biology, MedicineBritish Journal of Clinical Pharmacology
- 1 September 2003
An important role for both CYP3A4 and CYP2C8 in the human in vitro biotransformation of repaglinide is confirmed, which may have consequences for the clinical pharmacokinetics and drug-drug interactions involving repaglinside if one CYP pathway has sufficient capacity to compensate if the other is inhibited.
GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand
It is shown that GDF15 binds specifically to GDNF family receptor α-like (GFRAL) with high affinity, and that GFRAL requires association with the coreceptor RET to elicit intracellular signaling in response to GDF 15 stimulation.
Influence of Drugs Interacting with CYP3A4 on the Pharmacokinetics, Pharmacodynamics, and Safety of the Prandial Glucose Regulator Repaglinide
The pharmacokinetic profile of repaglinide was altered by administration of potent inhibitors or inducers, such as ketoconazole or rifampicin, but to a lesser degree than expected, while most adverse events were related to hypoglycemia, as expected in a normal population given a blood glucose regulator.
Absorption, metabolism and excretion of a single oral dose of 14C-repaglinide during repaglinide multiple dosing
- P. van Heiningen, V. Hatorp, J. Jonkman
- Medicine, BiologyEuropean Journal of Clinical Pharmacology
- 1 September 1999
After oral dosing with repaglinide, the mean peak plasma concentration was rapidly attained and, thereafter, plasma concentrations decreased promptly, making repaglinside a suitable insulin secretagogue for all patients with type-2 diabetes who retain sufficient β-cell function.
Xanomeline: A selective muscarinic agonist for the treatment of Alzheimer's disease
Xanomeline was found to be safe and reasonably well tolerated in safety studies in humans, and halted cognitive decline in patients with Alzheimer's disease, in a placebo controlled double blind clinical trial of 6 months duration.
Flavin-containing monooxygenase-mediated N-oxidation of the M(1)-muscarinic agonist xanomeline.
- B. Ring, S. Wrighton, S. Aldridge, K. Hansen, B. Haehner, L. Shipley
- Biology, MedicineDrug metabolism and disposition: the biological…
- 1 October 1999
The data and those in the literature suggest that the increased prevalence of N-oxidized metabolites of xanomeline after s.c. dosing as compared with oral dosing may be due to differences in the affinity of various FMO family members for xnomeline or to differencesIn exposure to xanmeline that these enzymes receive under different dosing regimens.
Butylthio[2.2.2] (NNC 11-1053/LY297802): an orally active muscarinic agonist analgesic.
- Michael D B Swedberg, M. Sheardown, H. Shannon
- Biology, ChemistryThe Journal of pharmacology and experimental…
- 1 May 1997
Data show that butylthio[2.2. 2] is a potent and efficacious antinociceptive with a very favorable therapeutic window after s.c. and p.o. administration in mice, and with good efficacy in rats.
PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopamine receptor
The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D1-dopamine receptor antagonists. Both compounds have been labeled with11C for examination by positron emission…
Pig hepatocytes as an in vitro model to study the regulation of human CYP3A4: prediction of drug-drug interactions with 17 alpha-ethynylestradiol.
Muscarinic analgesics with potent and selective effects on the gastrointestinal tract: potential application for the treatment of irritable bowel syndrome.
35, LY316108/NNC11-2192 was found to offer an exceptional profile combining analgesic potency in mouse writhing along with potency for normalization of GI motility, which suggests 35 as an excellent candidate for evaluation as a potential treatment of IBS.