Absorption, metabolism and excretion of [14C]gemigliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans.

1. Gemigliptin (formerly known as LC15-0444) is a newly developed dipeptidyl peptidase 4 inhibitor for the treatment of type 2 diabetes. Following oral administration of 50 mg (5.4 MBq) [(14)C]gemigliptin to healthy male subjects, absorption, metabolism and excretion were investigated. 2. A total of 90.5% of administered dose was recovered over 192 hr postdose, with 63.4% from urine and 27.1% from feces. Based on urinary recovery of radioactivity, a minimum 63.4% absorption from gastrointestinal tract could be confirmed. 3. Twenty-three metabolites were identified in plasma, urine and feces. In plasma, gemigliptin was the most abundant component accounting for 67.2% ∼ 100% of plasma radioactivity. LC15-0636, a hydroxylated metabolite of gemigliptin, was the only human metabolite with systemic exposure more than 10% of total drug-related exposure. Unchanged gemigliptin accounted for 44.8% ∼ 67.2% of urinary radioactivity and 27.7% ∼ 51.8% of fecal radioactivity. The elimination of gemigliptin was balanced between metabolism and excretion through urine and feces. CYP3A4 was identified as the dominant CYP isozyme converting gemigliptin to LC15-0636 in recombinant CYP/FMO enzymes.

Effects of Short-Term Differences in Concentrate Feeding on the Recovery of In Vivo Embryos in Hanwoo Donor Cows through Superovulation Treatment.

Superovulation is a technique used to increase the number of oocytes released for fertilization. This study investigated the effects of short-term differences in concentrate feed intake on in vivo embryo production through superovulation in indigenous Korean (Hanwoo) cows. The cows were given fresh water and hay ad libitum and randomly divided into three groups (control (CON, n = 9): 2.0 kg/day (unchanged diet); low concentrate (LC, n = 10): 0 kg/day; and high concentrate (HC, n = 8): 4.0 kg/day) according to the amount of formula they were fed. This feeding treatment began seven days before the start of the hormonal treatment for superovulation. From the results, the LC group had the greatest weight change and the lowest body condition score at harvest, followed by the CON and HC groups (p < 0.05). The LC group had the highest number of harvesting embryos, followed by the HC and CON groups (p < 0.05). Estradiol, progesterone, glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, total protein, and blood urea nitrogen concentrations did not differ between the groups, except for a temporary increase in the HC group on day 0. These findings suggest that more embryos may be harvested when short-term changes in concentrate intake are made during superovulatory responses in Hanwoo cows.

Effects of CYP2C9*3 and *13 alleles on the pharmacokinetics and pharmacodynamics of glipizide in healthy Korean subjects.

Glipizide is a second-generation sulfonylurea antidiabetic drug. It is principally metabolized to inactive metabolites by genetically polymorphic CYP2C9 enzyme. In this study, we investigated the effects of CYP2C9*3 and *13 variant alleles on the pharmacokinetics and pharmacodynamics of glipizide. Twenty-four healthy Korean volunteers (11 subjects with CYP2C9*1/*1, 8 subjects with CYP2C9*1/*3, and 5 subjects with CYP2C9*1/*13) were recruited for this study. They were administered a single oral dose of glipizide 5 mg. The plasma concentration of glipizide was quantified for pharmacokinetic analysis and plasma glucose and insulin concentrations were measured as pharmacodynamic parameters. The results represented that CYP2C9*3 and *13 alleles significantly affected the pharmacokinetics of glipizide. In subjects with CYP2C9*1/*3 and CYP2C9*1/*13 genotypes, the mean AUC0-∞ were increased by 44.8% and 58.2%, respectively (both P < 0.001), compared to those of subjects with CYP2C9*1/*1 genotype, while effects of glipizide on plasma glucose and insulin levels were not significantly different between CYP2C9 genotype groups. In conclusion, individuals carrying the defective CYP2C9*3 and CYP2C9*13 alleles have markedly elevated plasma concentrations of glipizide compared with CYP2C9*1/*1 wild-type.

Acerogenin C from Acer nikoense exhibits a neuroprotective effect in mouse hippocampal HT22 cell lines through the upregulation of Nrf-2/HO-1 signaling pathways.

Oxidative stress contributes to neuronal death in the brain, and neuronal death can cause aging or neurodegenerative disease. Heme oxygenase 1 (HO-1) serves a vital role in the regulation of biological reactions, including oxidative stress associated with reactive oxygen species. In the present study, acerogenin C isolated from the Aceraceae plant Acer nikoense, which is used as a Japanese folk medicine for hepatic disorders and eye diseases. However, there have been no studies on the mechanisms underlying the antineurodegenerative biological activities of acerogenin C. In the present study, acerogenin C demonstrated neuroprotective action against glutamate­induced cell death in hippocampal HT22 cells through the upregulation of HO­1 expression. These effects were also associated with nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the activation of phosphoinositide 3­kinase/protein kinase B. Taken together of the efficacy researches, this study determines that the Nrf2/HO­1 pathways denotes a biological mark and that acerogenin C might contribute to prevention of neurodegenerative disorders.