Synergism in Pharmacokinetics of Retagliptin and Metformin Observed during Clinical Trials of their Combination Therapy

Purpose: To investigate the safety and potential pharmacokinetic (PK) interaction between retagliptin, a selective inhibitor of dipeptidyl peptidase-4, and metformin in healthy subjects.Methods: In open-label, randomized, three-period, three-treatment crossover studies, 15 subjects received 100 mg retagliptin, 1500 mg metformin or the combination. The area under the curve from the time of dosing to infinity (AUCinf) and the maximum observed plasma concentration (Cmax) of each drug were measured.Results: The combination of retagliptin and metformin did not result in clinically significant alterations in the pharmacokinetics of SP2086 or metformin. The AUCinf and Cmax of retagliptin co-administered with metformin were 16.49 and 25.88 % higher than for retagliptin alone, respectively, while the AUCinf of metformin co-administered with retagliptin was 22.06 % higher than for metformin alone. The 90 % confidence interval of both glucose-lowering drugs’ AUCinf and Cmax of the geometric mean ratios of SP2086 + metformin fell within the pre-specified interval of 80 - 125 %. No laboratory adverse conditions occurred during the study. Retagliptin appeared generally safe and well-tolerated when administered alone or in combination with  metformin.Conclusion: The results may be an indication that no dose adjustments are likely to be required when retagliptin is given in combination with metformin

Effect of the Inhomogeneity of Ice Crystals on Retrieving Ice Cloud Optical Thickness and Effective Particle Size

Spherical or spheroidal air bubbles are generally trapped in the formation of rapidly growing ice crystals. In this study the single-scattering properties of inhomogeneous ice crystals containing air bubbles are investigated. Specifically, a computational model based on an improved geometric-optics method (IGOM) has been developed to simulate the scattering of light by randomly oriented hexagonal ice crystals containing spherical or spheroidal air bubbles. A combination of the ray-tracing technique and the Monte Carlo method is used. The effect of the air bubbles within ice crystals is to smooth the phase functions, diminish the 22deg and 46deg halo peaks, and substantially reduce the backscatter relative to bubble-free particles. These features vary with the number, sizes, locations and shapes of the air bubbles within ice crystals. Moreover, the asymmetry factors of inhomogeneous ice crystals decrease as the volume of air bubbles increases. Cloud reflectance lookup tables were generated at wavelengths 0.65 m and 2.13 m with different air-bubble conditions to examine the impact of the bubbles on retrieving ice cloud optical thickness and effective particle size. The reflectances simulated for inhomogeneous ice crystals are slightly larger than those computed for homogenous ice crystals at a wavelength of 0.65 microns. Thus, the retrieved cloud optical thicknesses are reduced by employing inhomogeneous ice cloud models. At a wavelength of 2.13 microns, including air bubbles in ice cloud models may also increase the reflectance. This effect implies that the retrieved effective particle sizes for inhomogeneous ice crystals are larger than those retrieved for homogeneous ice crystals, particularly, in the case of large air bubbles

Pathological changes and antigen localization in the small intestine of rabbits infected with Eimeria magna

[EN] Coccidiosis is a major disease caused by various Eimeria species in rabbits. The aim of the present study was to investigate the haematological and pathological changes in rabbits infected with E. magna. Moreover, the localisation of coccidial antigens was examined in the intestines of rabbits with two kinds of serum as primary antibodies. In the present study, forty-five 28-day-old weaned rabbits were randomly divided into three groups and reared in three separate places. Group A was infected with 20×103 sporulated oocysts of E. magna, group B was only used to produce anti-E. intestinalis serum by infecting them with 3×103 sporulated oocysts of E. intestinalis, and group C was designated as the control group. According to histopathological evaluation of group A, the epithelial cells of the jejunum and ileum were parasitised with a large number of oocysts and other stages of E. magna. The haematological results showed that red blood cell counts, haemoglobin counts, haematocrit levels and the percentage of lymphocytes were significantly decreased in group A compared with group C (P<0.01), but white blood cell counts and the percentage of neutrophils were significantly increased (P<0.01). The weight of group A began to decrease on the 5th day after infection, and this decrease continued until the 9th day. Immunohistochemistry staining revealed that two kinds of coccidial antigens were basically located at the same sites of the intestine when anti-E. intestinalis serum and anti-E. magna serum were used as primary antibodies. Most likely, E. magna and E. intestinalis antigens have some similar antigenic determinants; this finding provides a theoretical basis for screening for common antigens of these two coccidian species.This study was supported by grants from the National Natural Science Foundation Project of China (nos.31960688 and 31360592) and the Natural Science Foundation Project of Jiangxi Province (no. 20181BAB204016).Yuan, X.; Liu, J.; Wang, F.; Hu, XF.; Wen, F.; Tang, XE.; Yang, SS.... (2021). Pathological changes and antigen localization in the small intestine of rabbits infected with Eimeria magna. World Rabbit Science. 29(3):183-192. http://hdl.handle.net/10251/173608OJS18319229