Bioequivalence of daclatasvir hydrochloride tablets in healthy Chinese subjects.

OBJECTIVE: The aim of the present study was to evaluate the bioequivalence and safety of two types of daclatasvir hydrochloride tablets administered to healthy Chinese subjects under fasting and postprandial conditions. MATERIALS AND METHODS: A total of 72 healthy Chinese subjects were randomly divided into two groups: the fasting group (n = 36) and the postprandial group (n = 36). A dose of 60 mg of both the test and reference preparations of the daclatasvir hydrochloride tablets was taken orally under fasting and postprandial conditions. RESULTS: The main plasma pharmacokinetic parameters of the test and reference preparations in the fasting group were as follows: T1/2 was 9.82 ± 1.00 and 9.67 ± 0.99 hours, respectively; tmax was 1.00 hour in both; Cmax was 1,528.25 ± 428.80 and 1,504.25 ± 414.50 ng/mL-1, respectively; AUC0-t was 14,553.04 ± 4,013.26 and 14,391.97 ± 4,078.18 h/ng/mL-1, respectively; the AUC0-∞ was 14,660.80 ± 4,018.37 and 14,494.85 ± 4,095.57 ng/mL-1, respectively. Meanwhile, the main plasma pharmacokinetic parameters of the test and reference preparations in the postprandial group were as follows: T1/2 was 10.18 ± 1.38 and 10.18 ± 1.69 hours, respectively; tmax was 2.00 and 1.75 hours, respectively; Cmax was 974.92 ± 248.50 and 981.44 ± 237.11 ng/mL-1, respectively; AUC0-t was 9,597.00 ± 3,094.28 and 9,982.83 ± 3,512.07 h/ng/mL-1, respectively; AUC0-∞ was 9,712.92 ± 3,130.43 and 10,113.97 ± 3,593.47 ng/mL-1, respectively. CONCLUSION: Both types of daclatasvir hydrochloride tablets demonstrated good safety levels in healthy Chinese subjects under both fasting and postprandial conditions. Moreover, the two preparations were bioequivalent.

[Safety and Tolerance of Healthy People to Injection of Astragalosides-a New Drug for Coronary Heart Disease].

OBJECTIVES: To assess the safety and tolerance of healthy volunteers to as tragalosides injection (AGI), and to determine a safe dose range for phase II clinical trial. METHODS: A total of 62 healthy volunteers participated in this study, with 26 being given a single AGI of 100 mL, 200 mL, 300 mL, 400 mL, 500 mL, or 600 mL and 36 subjects being given 500 mL, 400 mL, 200 mL or 300 mL of AGI once a day for 7 d. Discomfortsymptoms, vital signs and safety problems were recorded 3 d and 7 d after the administration of AGI. The results were analyzed. RESULTS: Of the 62 participants, 40 adverse events (AEs) were reported by 31 participants, which included 23 mild adverse reactions (ADRs) and 4 moderate ADRs. Nine AEs were reported by 9 participants with single AGI, including 7 ADRs. Fourteen AEs were reported by 10 participants with 500 mL and 400 mL multiple AGI, including 12 ADRs occurred in 9 participants.Seventeen AEs were reported by 12 participants with 300 mL and 300 mL multiple AGI, including 3 mild ADRs. The main ADRs included abnormal liver function [slightly elevated glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST),and serum total bilirubin (TBil)], low blood potassium, increased urine red blood cell count, rash, and phlebitis. CONCLUSIONS: The maximum tolerance is 600 mL for single-dose treatment, and 400 mL for multiple-dose (7 d). The dose guidance given in this study should be examined its effects and safety in patients with coronary heart disease in phase II clinical trial.

Synthesis, optical properties and preliminary in vitro photodynamic effect of pyridyl and quinoxalyl substituted chlorins.

A series of chlorophyll a-based chlorins conjugated with pyridyl or quinoxalyl group at different positions were synthesized, characterized and evaluated for their photodynamic effect in vitro. It was found that all the pyridyl and quinoxalyl chlorins showed promising photocytotoxicities but nontoxic without irradiation in HeLa cells, and the substituted types and positions had a significant influence on the photocytotoxicities of the chlorophyll a-based chlorins. All the chlorins with a pyridyl group at the C-D ring end exhibited relatively high photocytotoxicity as compared to those with 3(2)-pyridyl. Among them, compound 12 conjugated with a pyridyl group at its C12 position showed the best photodynamic effect in HeLa cells with an IC50 value of 0.033µM. These facts, associated with the relative high long wavelength absorptions of those chlorins may provide valuable ways to design and prepare promising photosensitizers for application in photodynamic therapy.

Highly efficient synthesis of novel methyl 13(2)-methylene mesopyropheophorbide a and its stereoselective Michael addition reaction.

Treatment of methyl mesopyropheophorbide a with formaldehyde under basic conditions gave a novel 13(2)-methylene derivative in 85% yield; under acidic conditions, the corresponding 20-hydroxymethyl derivative was obtained in 65% yield. The high reactivity of the enone structural motif existed in the former product provides a unique way to construct some novel chlorophyll a derivatives for various applications. Stereoselective Michael reaction of this compound is studied and discussed.

Pharmacokinetic profiles of hydroxysafflor yellow A following intravenous administration of its pure preparations in healthy Chinese volunteers.

ETHNOPHARMACOLOGICAL RELEVANCE: Hydroxysafflor yellow A (HSYA), the major active marker compound isolated from Carthamus tinctorius L., has been demonstrated to possess various attractive pharmacological activities. However, there is a lack of information about the complete clinical pharmacokinetic profiles of HSYA following the administration of its pure preparations. The purpose of this study was to fully characterize the pharmacokinetic (PK) properties of HSYA in healthy Chinese volunteers following drip intravenous infusion of injectable powder of pure HSYA (IPPH), a new drug recently approved for the phase I clinical study by China Food and Drug Administration. MATERIALS AND METHODS: 36 healthy subjects of either sex were recruited in this single-center, and open-label, single doses (25, 50, and 75 mg) and multiple doses (50 mg, once daily, 7 consecutive days) study. Plasma samples were analyzed with a validated LC-MS/MS method. Various PK parameters were estimated from the plasma concentration versus time data using non-compartmental methods. RESULTS: After single dose administration of IPPH, the values of AUC(0-t), AUC(0-∞) and C(max) for HSYA were statistically proportional over the dose range of 25-75 mg. After 7 repeated doses of 50 mg IPPH, both C(max) and AUC(0-∞) were significantly decreased, from 3207 to 2959 µg L(-1), and from 12,811 to 12,135 µg h L(-1) respectively, while t(1/2) was significantly prolonged from 3.912 to 4.414 h. The minimum plasma concentrations on day 5, 6 and 7 showed good stability with no significant difference. Both Cmax and AUC of HSYA in male volunteers were generally lower than that in females. IPPH was generally well tolerated in healthy volunteers by either single or multiple dosing. CONCLUSION: HSYA displayed moderately linear PK properties over the doses ranging from 25 to 75 mg of IPPH. Repeated administration of IPPH once daily could not lead to the in-vivo drug accumulation, but significantly affect PK behavior of HSYA. Gender difference should be considered for dosage recommendation in the clinic.

A new iridoid and other chemical constituents from Pedicularis kansuensis forma albiflora Li.

A new iridoid (1) and thirteen known compounds 2-14 were isolated from Pedicularis kansuensis forma albiflora Li., and their structures were elucidated by spectroscopic methods including 2D-NMR techniques.