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.

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.