Pharmacokinetics of pilsicainide hydrochloride for injection in healthy Chinese volunteers: a randomized, parallel-group, open-label, single-dose study.

BACKGROUND: Pilsicainide hydrochloride is a class IC antiarrhythmic agent used for the treatment of supraventricular and ventricular arrhythmias and atrial fibrillation. OBJECTIVE: The objective of the present study was to determine the pharmacokinetics (PK) of a pilsicainide hydrochloride injection in healthy Chinese adults. The study was conducted to meet China State Food and Drug Administration requirements for the marketing of the new generic formulation of pilsicainide hydrochloride. METHODS: This Phase I, randomized, parallel-group, open-label, single-dose PK study was conducted in healthy Chinese volunteers. Subjects were randomized to receive a single dose of 0.25-, 0.50-, and 0.75-mg/kg pilsicainide hydrochloride with a 10-minute intravenous infusion. Serial blood and urine samples were collected up to 24 hours after dosing; drug concentrations in plasma and urine were then determined by using LC-MS/MS. The PK parameters of pilsicainide were calculated from the plasma concentration-time data according to noncompartmental methods. Safety profile was evaluated by monitoring adverse events, clinical laboratory parameters, and the results of 12-lead ECGs. RESULTS: Thirty healthy volunteers (mean [SD] age, 28.0 [4.95] years; weight, 59.3 [6.51] kg; height, 165.0 [7.25] cm; body mass index, 21.7 [1.94] kg/m(2)) were randomly divided into 3 groups, each consisting of 5 men and 5 women. After single-dose intravenous administration of 0.25, 0.50, and 0.75 mg/kg of pilsicainide hydrochloride, mean Cmax was 0.34 (0.11), 0.54 (0.15), and 1.05 (0.19) µg/mL, respectively; AUC0-24 was 0.76 (0.12), 1.61 (0.37), and 2.61 (0.46) h · µg/mL; and AUC0-∞ was 0.79 (0.13), 1.71 (0.46), and 2.72 (0.50) h · µg/mL. The ranges for t½z, CL, and Vz were 5.19 to 5.98 hours, 4.73 to 5.44 mL/min/kg, and 2.23 to 0.58 L/kg, respectively. The mean urinary recovery rate within 24 hours was 75.0% (12.0%), 65.0% (19.2%), and 66.4% (14.1%). Men and women had significantly different AUC0-24 values in the 0.50-mg/kg dose group (P = 0.044), and Vz showed significant differences between men and women in all 3 dose groups (P = 0.001). According to ECG parameters, PR intervals were significantly prolonged after administration at all 3 doses (P = 0.034, P < 0.001, and P = 0.034); no significant changes were seen in QRS width, QTc interval, or other parameters. CONCLUSIONS: Pilsicainide hydrochloride demonstrated linear PK, and the increase in the exposure of pilsicainide (AUC0-24 and AUC0-∞) was dose proportional after single doses of 0.25, 0.50, and 0.75 mg/kg. All 3 pilsicainide hydrochloride doses were well tolerated in these Chinese volunteers. ChiCTR-ONC-13003546.

[Spectroscopic characterization analysis on Cr (VI) removal mechanism by low-cost adsorbent of rice husk ash].

Analyzing methods of Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction analysis (XRD) and X-ray fluorescence spectroscopy (XRF) were used to reveal the adsorption mechanism of Cr(VI) by low-cost adsorbent of rice husk ash. Results of FTIR showed that amide II band, Si--O--Si, and (O--Si--O were important for Cr(VI) removal. SEM micrographs suggested that series of needle-shaped precipitation appeared on cell surface, and inorganic precipitation mechanism and redox mechanism might work in the test. XPS spectra showed that main elements of rice husk ash were C, N, O, P and Si, existing state of C was mainly aldoketones groups, coordi nation reaction existed between C functional groups and Cr(VI); N element, --NH2 in chief, could remove Cr(VI) in the way of physical adsorption based on electrostatic interaction; Si--O might be useful in adsorption process. XRD data suggested representative characteristic adsorption band of SiO2, and the increasing crystallinity of rice husk ash showed metallic compound formed between Cr(VI) and rice husk ash. XRF results indicated that the content of K, Na, Mg and Ca changed, and two new elements were detected, the evidence of ion exchange mechanism. The functional groups played different roles in Cr(VI) adsorption process, and inorganic precipitation mechanism, redox mechanism, surf-complexation mechanism and ion exchange mechanism were important ways in Cr(VI) removal, which could provide theoretical support in further application.