Pharmacokinetics, mass balance, and metabolism of [14C]vicagrel, a novel irreversible P2Y12 inhibitor in humans.

Vicagrel, a novel irreversible P2Y12 receptor inhibitor, is undergoing phase III trials for the treatment of acute coronary syndromes in China. In this study, we evaluated the pharmacokinetics, mass balance, and metabolism of vicagrel in six healthy male Chinese subjects after a single oral dose of 20 mg [14C]vicagrel (120 µCi). Vicagrel absorption was fast (Tmax = 0.625 h), and the mean t1/2 of vicagrel-related components was ~38.0 h in both plasma and blood. The blood-to-plasma radioactivity AUCinf ratio was 0.55, suggesting preferential distribution of drug-related material in plasma. At 168 h after oral administration, the mean cumulative excreted radioactivity was 96.71% of the dose, including 68.03% in urine and 28.67% in feces. A total of 22 metabolites were identified, and the parent vicagrel was not detected in plasma, urine, or feces. The most important metabolic spot of vicagrel was on the thiophene ring. In plasma pretreated with the derivatization reagent, M9-2, which is a methylated metabolite after thiophene ring opening, was the predominant drug-related component, accounting for 39.43% of the radioactivity in pooled AUC0-8 h plasma. M4, a mono-oxidation metabolite upon ring-opening, was the most abundant metabolite in urine, accounting for 16.25% of the dose, followed by M3-1, accounting for 12.59% of the dose. By comparison, M21 was the major metabolite in feces, accounting for 6.81% of the dose. Overall, renal elimination plays a crucial role in vicagrel disposition, and the thiophene ring is the predominant metabolic site.

Glycerol-3-phosphate metabolism plays a role in stress response in the red alga Pyropia haitanensis.

Glycerol-3-phosphate (G3P) has been suggested as a novel regulator of plant defense signaling, however, its role in algal resistance remains largely unknown. The glycerol kinase (also designated as NHO1) and NAD-dependent G3P dehydrogenase (GPDH) are two key enzymes involved in the G3P biosynthesis. In our study, we cloned the full-length cDNA of NHO1 (NHO1Ph ) and GPDH (GPDHP h ) from the red alga Pyropia haitanensis (denoted as NHO1Ph and GPDHP h ) and examined their expression level under flagellin peptide 22 (flg22) stimulation or heat stress. We also measured the level of G3P and floridoside (a downstream product of G3P in P. haitanensis) under flg22 stimulation or heat stress. Both NHO1Ph and GPDHP h shared high sequence identity and structural conservation with their orthologs from different species, especially from red algae. Phylogenetic analysis showed that NHO1s and GPDHs from red algae were closely related to those from animals. Under flg22 stimulation or heat stress, the expression levels of NHO1Ph and GPDHP h were up-regulated, G3P levels increased, and the contents of floridoside decreased. But the floridoside level increased in the recovery period after heat stress. Taken together, we found that G3P metabolism was associated with the flg22-induced defense response and heat stress response in P. haitanensis, indicating the general conservation of defense response in angiosperms and algae. Furthermore, floridoside might also participate in the stress resistance of P. haitanensis.

[Advances on the genome of algae].

Algae possess complex and diverse biology and evolutionary history. They play an important role in the ecosystem. A mass of unique genes and biological processes also make them attractive. The application of high-throughput sequencing approaches to algal research has greatly contributed to the development of algal genomics and transcriptomics, as well as enriched the gene information of algae. In this article, we summarize the advances of algal genomics and transcriptomics, describe and compare the characteristics of different algae genomes, and introduce the application of expression sequence tags (ESTs), microarray and RNA sequencing technique to algal transcriptomics research. Furthermore, the advances of algal gene expression and small RNA are also reviewed in detail. At last, we discuss the challenges and future development of this area.

Comparative pharmacokinetic and bioavailability studies of three salvianolic acids after the administration of Salviae miltiorrhizae alone or with synthetical borneol in rats.

Salviae miltiorrhizae is one of the most commonly used herbal plants in the treatment of numerous ailments including cardiovascular diseases for hundreds of years. According to the theory of traditional Chinese herbal medicine, S. miltiorrhizae is always used in combination with borneol to obtain better pharmacological effects. The purpose of this study was to investigate the effects of borneol on the pharmacokinetic and bioavailability of S. miltiorrhizae. The pharmacokinetics studying on rosmarinic acid, salvianolic acid A and salvianolic acid B which are the main active compounds of S. miltiorrhizae in rat plasma, was achieved using a optimal high-performance liquid chromatographic technique coupled with liquid-liquid extraction method. After administration of either single salvianolic acids or salvianolic acids in combination with borneol, plasma concentrations of rosmarinic acid, salvianolic acid A and salvianolic acid B of male Sprague-Dawley rats were determined at different time points (5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, and 360 min). In comparison with salvianolic acid extract alone, there were statistically significant differences in pharmacokinetic parameters of rosmarinic acid, salvianolic acid B and salvianolic acid A, and the bioavailability of the three salvianolic acids increased by different degrees when the salvianolic acid extract and borneol were administered together. These results indicated that borneol could enhance the intestinal absorption, decrease the distribution and inhibit the metabolism of salvianolic acids.

[Intestinal absorption properties of three components in salvianolic acid extract and the effect of borneol on their absorption in rats].

This study aimed to investigate the effects of concentration, intestinal section and borneol on the intestinal absorption of salvianolic acids. The experiment not only studied the intestinal absorption properties of three concentrations of rosmarinic acid, salvianolic acid B and salvianolic acid A at duodenum, jejunum and ileum, but also of salvianolic acids compatible with borneol at different concentrations using single-pass intestinal perfusion model in rat with phenol red as the marker. The results showed that salvianolic acids was stable under weak-acid condition and affected by metabolism enzyme; The Peff and Ka significantly different among three concentrations of rosmarinic acid and salvianolic acid B, whose intestinal absorption were saturated in high concentration, suggesting that the transport mechanisms of rosmarinic acid and salvianolic acid B were similar to active transport or facilitated diffusion; However, there was inconspicuousness in the Peff and Ka of salvianolic acid A at different concentrations, whose absorption was not saturated in high concentration, indicating that the transport mechanisms of salvianolic acid A was passive diffusion; The Peff and Ka in the ileum obviously higher than those in the duodenum and jejunum, namely the ileum was the best absorption section; When concentration of borneol increased, the enhancing effect of intestinal absorption of salvianolic acids increased, but significantly decreased when borneol increased to some degree. The enhancing effect of medium borneol concentration was the optimum. This implied that borneol can enhance the intestinal absorption of salvianolic acids, and the capacity of enhancing effect was influenced by the concentration of borneol.