Comparison of Pharmacokinetics and Bioavailability of Fixed-Dose Combination Tablet and Monotherapy Combination of Allisartan Isoproxil and Indapamide Sustained-Release in Healthy Chinese Volunteers.

This study aimed to compare the pharmacokinetics and bioavailability of 2 formulations: a fixed-dose combination tablet containing allisartan isoproxil (AI) and indapamide sustained-release (SR), and a monotherapy combination of AI and indapamide SR, in healthy Chinese subjects. A monocentric, open-label, single-dose, randomized, 2-way crossover study design was implemented. A total of 38 healthy male and female volunteers were equally divided into 2 treatment sequences. The analysis of plasma concentrations was conducted using a nonstereospecific liquid chromatography/tandem mass spectrometric method. The primary pharmacokinetic parameters were calculated using a noncompartmental model. Safety assessments were performed throughout the study. For the fixed-dose combination and monotherapy combination, the mean values of EXP3174 (metabolite of AI) Cmax , AUC0-t , and AUC0-∞ were 987 and 999 ng/mL, 8059 and 7749 ng/mL h, and 8332 and 8007 ng/mL h, respectively. The corresponding values for indapamide were 27 and 32 ng/mL, 1002 and 1105 ng/mL h, and 1080 and 1172 ng/mL h. No serious adverse events were reported during the study. The combination tablet containing 240 mg of AI and 1.5 mg of indapamide SR met the bioequivalence standards. Additionally, both formulations were tolerated and had good safety profiles in the research.

Expressions of IFNγ,IP-10 and CXCR3 in infection-associated hemophagocytic syndrome and their clinical significance / 中华临床感染病杂志

Objective To investigate the expressions of interferon γ(IFNγ), interferon inducible protein-10(IP-10). chemokine receptor CXCR3 and their significance in infection-associated hemophagocytic syndrome(IAHPS). Methods Forty-three patients with IAHPS, 35 infection patients without HPS and 25 healthy controls were included in the study. The serum IFNγ and IP-10 levels were measured by enzyme linked immunosorbent assay(ELISA). The expression of CXCR3 on cell surface of CD_4~+ and CD_8~+ T cells in peripheral blood was determined by flow cytometry. SPSS 13.0 was used for data processing, and independent-sample t test was performed to compare the differences among the groups. Results The serum IFNγ and IP-10 levels in patients with IAHPS were( 608±135) pmol/L and(939±141) pmol/L respectively, which were significantly higher than those in without HPS group[(154±45) pmol/L and (385±119) pmol/L, t=4.97 and 4.02, P<0.05] and healthy controls[(56±18) pmol/L and (248±98) pmol/L, t=5.27 and 4.77, P<0.05]. The expressions of CXCR3 on CD_4~+ and CD_8~+ T cells in IAHPS group were (35±11)% and (23±8)% respectively, which were significantly higher than those in without HPS group[(24±7)% and (16±7)%, t=3.12 and 3.62, P<0.05] and healthy controls[(20±6)% and (12±5)%, t=4.46 and 4.93, P<0.05]. Conclusion The expressions of IFNγ, IP-10 and CXCR3 are increased significantly in patients with IAHPS, which may be related to the disease pathogenesis.

Homoharringtonine mediates myeloid cell apoptosis via upregulation of pro-apoptotic bax and inducing caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP).

Homoharringtonine (HHT) is a plant alkaloid with antileukemia activity that is currently being used for treatment of acute, chronic leukemias and MDS. In this study, we show that HHT can induce apoptosis in a variety of human myeloid leukemia cell lines (U937, HL-60, HEL, THP, and K562). U937 and HL60 cells undergo rapid apoptosis on treatment with HHT, as indicated by increased annexin V binding capacity, caspase-3 activation, and cleavage of poly(ADP-ribose) polymerase (PARP). In addition, the expression of bax is upregulated during HHT-induced cell death, whereas the expression of bcl-2 is only slightly decreased. Importantly, treatment of primary leukemic cells, obtained from acute myeloid leukemia patients, resulted in rapid apoptosis. Thus, our data provide the mechanism of HHT and justify the use of HHT in the treatment of human myeloid leukemia.