Zhen Zhang

Background and Objective Helicobacter pylori-positive ulcers are treated with a proton pump inhibitor (PPI) + two antibiotics with/without bismuth. The objective of this study was to investigate the pharmacokinetic interaction of the novel PPI anaprazole, amoxicillin and clarithromycin with/without bismuth. Methods This single-centre, randomised, open-label phase 1 pharmacokinetic study included healthy Chinese male participants, comprising two cohorts (cohort 1, 4 × 4 crossover design; cohort 2, 2 × 2 crossover design). In cohort 1, 24 participants received four treatment cycles with a different treatment in each cycle; the washout period between cycles was 9 days. Participants were randomly assigned to one of the following four treatment sequences (1:1:1:1): anaprazole sodium enteric-coated tablet 20 mg monotherapy, amoxicillin 1000 mg monotherapy, clarithromycin 500 mg monotherapy, and a three-drug combination (anaprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg). During each treatment cycle, study drugs were administered twice daily for four consecutive days and once in the morning on the fifth day. Cohort 2 participants were administered a single dose of the three-drug combination and a single dose of a four-drug combination (three-drug combination + bismuth 0.6 g) with a washout period of 11 ± 2 days between treatments. Blood samples were collected for pharmacokinetic analysis. Results Twenty-nine of 32 enrolled participants (cohort 1, n = 24; cohort 2, n = 8) completed the study. There were no significant differences in exposure or time to reach maximum concentration (T_max) between each single drug or the three-drug combination (cohort 1) or between the three- and four-drug combinations (cohort 1) for any of the drugs/metabolites. Conclusions Dose adjustments for individual drugs are not necessary with combined dosing of anaprazole, amoxicillin, clarithromycin and bismuth.

Radix Salvia miltiorrhiza (Danshen) and Radix Puerariae lobatae (Gegen) are used in Traditional Chinese Medicine to treat cardiovascular diseases. However, adverse herb-drug interactions were observed between warfarin and herbal remedies containing Danshen and Gegen. This study aims to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and the different components found in Danshen and Gegen. Sixty Sprague–Dawley rats were used to investigate the effects of warfarin (0.2 mg/kg), Danshen (240 or 480 mg/kg) and Gegen (240 or 480 mg/kg) both in isolation and combination. The rats in the warfarin and Danshen/Gegen combination groups were given an oral dose of Danshen or Gegen 2 h after being given an oral dose of warfarin. After five consecutive days of treatment, the pharmacokinetic interactions between Danshen/Gegen and warfarin were investigated by simultaneously monitoring and comparing the cytochrome P450 (CYP) activities, mRNA and protein expression levels in the livers of the rats from the different treatment groups. The pharmacodynamic interactions were evaluated by monitoring and comparing the vitamin K epoxide reductase (VKOR) activities, mRNA and protein expression levels in the livers of rats from the different groups, as well as the thrombomodulin (TM) activities, mRNA and protein in the lungs of these animals. The rat plasma soluble thrombomodulin concentrations of the different treatment groups were also evaluated. Microsomes incubation, Real Time-Polymerase Chain Reaction and Western blot was applied respectively to study the activity, mRNA expression and protein expression of CYP, VKOR and TM. The activities and expression levels of the CYP and VKOR enzymes in the warfarin-Gegen combination groups increased by nearly 30 % (P = 0.02) compared with the warfarin-alone group, whereas those of TM decreased by almost 25 % (P = 0.02). The administration of Danshen did not lead to any changes in the activities or the expression levels of the CYP, VKOR or TM enzymes compared with those of the control group. Gegen induced several warfarin-metabolizing CYP enzymes and neutralized the effects of warfarin towards VKOR and TM. Gegen, rather than Danshen at the same tested dosage, offsets the anticoagulant effects of warfarin by accelerating the phase I liver metabolism of warfarin, as well as increasing the activity, mRNA and protein expression of VKOR while decreasing those of TM.

Background: The G-protein-coupled receptor (GPCR) superfamily represents the largest protein family in the human genome. These proteins have a variety of physiological functions that give them well recognized roles in clinical medicine. InXenopus tropicalis, a widely used animal model for physiology research, the repertoire of GPCRs may help link the GPCR evolutionary history in vertebrates from teleost fish to mammals.Results: We have identified 1452 GPCRs in theX. tropicalisgenome. Phylogenetic analyses classified these receptors into the following seven families:Glutamate,Rhodopsin,Adhesion,Frizzled,Secretin,Taste 2andVomeronasal 1. Nearly 70% ofX. tropicalisGPCRs are represented by the following three types of receptors thought to receive chemosensory information from the outside world: olfactory, vomeronasal 1 and vomeronasal 2 receptors.Conclusion: X. tropicalisshares a more similar repertoire of GPCRs with mammals than it does with fish. An examination of the three major groups of receptors related to olfactory/pheromone detection shows that inX. tropicalis, these groups have undergone lineage specific expansion. A comparison of GPCRs inX. tropicalis, teleost fish and mammals reveals the GPCR evolutionary history in vertebrates.