Reference

Single-dose oral toxicity study of AY4166 in rats

Single-dose oral toxicity study of AY4166 in rats. Hasegawa, Kazuo; Oguihara, Sadahiko; Miwa, Tadashi; Higuchi, Kiriko; Kikuchi, Tomoko; Tsubuku, Shoji (Life Sci. Lab.Several substances are used for example 105816-04-4 which is its cas registry number., Central Res. Lab., Ajinomoto Co., Inc., Japan). Yakuri to Chiryo, 25(Suppl. 1), S/5-S/8 (Japanese) 1997 Raifu Saiensu Shuppan K.K. CODEN: YACHDS. ISSN: 0386-3603. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The hypoglycemic drug AY4166, suspended in Me cellulose, was administered once to male and female Crj: CD(SD) rats by gavage at 0.5, 1.0, or 2.0 g/kg. There were no deaths among the animals during the study. Signs of acute toxicity were obsd. approx. 3 h after administration. Diarrhea occurred in females receiving 30.5 g/kg, and in the animals receiving 2.0 g/kg, decreased locomotor movement, hunchback position, and closed eyes were obsd. Lowered body wt. gain, possibly due to a transient decrease in food intake, was obsd. in female rats 2 days after receiving 2.0 g/kg. Wt. gain was soon recovered. No histopathol. changes were found. Based on these findings, the LD of AY4166 was considered to be >2.0 g/kg. .

Effect of a selective CYP2C9 inhibitor on the pharmacokinetics of nateglinide in healthy subjects

Effect of a selective CYP2C9 inhibitor on the pharmacokinetics of nateglinide in healthy subjects. Sabia, Helene; Sunkara, Gangadhar; Ligueros-Saylan, Monica; Wang, Yibin; Smith, Harold; McLeod, James; Prasad, Pratapa (Exploratory Clinical Development, Novartis Pharmaceuticals, East Hanover, NJ 07936-1080, USA). European Journal of Clinical Pharmacology, 60(6), 407-412 (English) 2004 Springer GmbH. CODEN: EJCPAS. ISSN: 0031-6970. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Purpose: The objective of the study was to det. the effect of a potent and selective CYP2C9 inhibitor, sulfinpyrazone (Anturane), on the pharmacokinetics of nateglinide (Starlix), a novel antidiabetic drug which is primarily (70%) metabolized via CYP2C9. Methods: This was a randomized, open-label, two-period, crossover study in 18 healthy volunteers. 329978-01-0 and 105816-04-4 are cas registry numbers. These chemicals are also mentioned in this article. Nateglinide was administered as a single 120-mg oral dose alone (ref.) on day 1 or in combination with sulfinpyrazone (test) on day 7, following twice-daily 200-mg oral doses (i.e., 400 mg/day) of sulfinpyrazone for 7 days. Pharmacokinetic parameters of nateglinide were detd. following the administration of nateglinide alone, and when administered in combination with sulfinpyrazone. Plasma nateglinide concns. were detd. using a validated high-performance liq. chromatog. method. Results: The administration of nateglinide in combination with sulfinpyrazone resulted in 28% higher mean AUC of nateglinide (90% CI for test-ref. ratio: 1.20-1.39) with no differences in mean peak plasma concn. (Cmax; 90% CI test-ref. ratio: 0.86-1.12) compared with nateglinide-alone treatment. The time to reach Cmax (tmax) and the elimination half-life of nateglinide were similar between the two treatments. Both treatments were safe and well tolerated. Conclusions: Sulfinpyrazone increased the mean exposure of nateglinide by 28% when both drugs were administered in combination. Nateglinide, given as a single dose or co-administered with multiple doses of sulfinpyrazone, was safe and well tolerated in healthy subjects. .