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The present study aimed to evaluate the pharmacokinetic properties and antiplatelet aggregation activity of eptifibatide in healthy Chinese subjects. Eptifibatide (180 μg/kg) was administrated by 2 bolus injections 10 minutes apart, followed by a 2.0 μg/kg/min infusion for 24 hours. The eptifibatide pharmacokinetic and antiplatelet aggregation activities were evaluated using nonlinear mixed‐effects modeling and noncompartmental analysis. Safety assessments included adverse events, hematology, and biochemistry tests. Twelve Chinese healthy subjects were enrolled and completed the study. Steady‐state concentrations were achieved at 0.5 to 24 hours after dosing. The median time to maximum concentration was 13 minutes, and the mean terminal elimination half‐life was 148.19 minutes. The effective inhibition of platelet aggregation (<20% platelet aggregation) occurred by 3 minutes after starting dosing to 4 hours after termination of the infusion. Eptifibatide concentrations were fitted with a 3‐compartment model, and the typical value of clearance was 0.11 L/min, with no significant covariates found. Three mild adverse events were detected in the study. Eptifibatide displays high sensitivity and excellent tolerability in healthy Chinese subjects. The dosage of eptifibatide recommended on the label for whites can effectively inhibit platelet aggregation. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to explore the association of pharmacokinetic variability and pharmacogenomics with the bioequivalence of orally administered gefitinib (Iressa®, AstraZeneca) provided by three sponsors in healthy subjects. Methods: The study designs were randomized, open-label, and two-period crossover studies in both fasting and fed healthy subjects. In one fasting study, the sample size was enlarged from 30 to 60 for the failing study. Each study subject received a 250-mg gefitinib tablet with a 21-day washout. The plasma concentrations were measured using LC-MS/MS, and pharmacokinetic parameters were determined by noncompartmental methods. Genetic analyses of CYP3A4, CYP3A5, and CYP2D6 alleles were carried out by the polymerase chain reaction (PCR). Results: Two hundred and sixty healthy male subjects were enrolled. The median maximum plasma concentration (Tmax) was 4–5 h, and the mean elimination half-life (t1/2) was 18–26 h. The maximum plasma concentration (Cmax) and area under the curve (AUC) increased but Tmax and t1/2 were unaffected by the intake of high-fat food. Three fed and two fasting studies achieved a plausible bioequivalence. The intake of high-fat food decreased the intra-subject variability significantly. In addition, CYP2D6 was associated with gefitinib exposure and may contribute to the high inter-subject variability, but it did not influence the bioequivalence result. Conclusions: Gefitinib is well tolerated, and the bioequivalence is easier to achieve under fed conditions compared to fasting conditions. The 90% confidence interval (CI) of geometric mean ratio (GMR) can be narrowed when the sample size is enlarged without changing the formulation-related technology. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Yimitasvir phosphate, an inhibitor of nonstructural protein 5A (NS5A) replication complex of hepatitis C virus (HCV), was evaluated in a double‐blind, placebo‐controlled, parallel, multiple‐dose study. Methods: Twenty‐four patients with chronic HCV genotype 1 infection were randomized to receive a 7‐day course of yimitasvir phosphate at daily doses of 30, 100 or 200 mg or placebo. Antiviral efficacy, resistance profile, pharmacokinetics (PK), safety and tolerability were assessed. Key findings: The maximal reduction in HCV RNA from baseline was 5.17 log10 IU/ml. However, most patients experienced viral rebound on or before day 3 after yimitasvir treatment was initiated. The PK profile revealed median peak plasma concentrations at 4–12 h postdose and a mean terminal half‐life of 14.47–17.09 h, the basis for daily dosing. Steady drug state was achieved following 5 days of daily dosing. The accumulation rate was low (1.29–1.73). There were no significant alterations in vital signs and laboratory findings among all participants. Conclusions: This study shows that yimitasvir phosphate was well tolerated, and the PK profile supported daily dosing regimens. A 1‐week (7‐day) treatment course led to a quick and significant reduction in HCV RNA level in this cohort with HCV GT‐1 infection. [ABSTRACT FROM AUTHOR]

Aims A recombinant human serum albumin-interferon alpha2a fusion protein (rHSA/IFNα2a) is expected to extend the half-life of IFNα2a. This study aims to evaluate the tolerability, safety and efficacy of rHSA/IFNα2a. Methods This is an open, randomized, positive control, multiple-dose ascending Phase Ib study. A panel of 32 treatment naïve and non-cirrhotic chronic hepatitis B patients were divided into four cohorts, and each received 600, 750 or 900 μg of rHSA/IFNα2a or 180 μg of PEG-IFNα2a for 3 months. Tolerability, pharmacokinetics and antiviral responses were assessed. Results Thirty-one of 32 enrolled patients completed the treatment study. The rHSA/IFNα2a treatment was better tolerated than the PEG-IFNα2a 180 μg treatment, as evidenced by blood cell counts and higher serum albumin levels. Half-life ( t1/2) of rHSA/IFNα2a was estimated to be 120-140 h, and is potentially suitable for a dosing interval of 2 weeks or longer. Pharmacokinetics of the last dose between rHSA/IFNα2a 750 μg and PEG-IFNα2a 180 μg, with the exception of t1/2, was comparable, and a similar kinetics of inhibiting HBV DNA replication was observed in both groups. Mean reductions in serum HBV DNA levels after treatment were −1.32, −2.13, −1.10 and −2.48 log10 IU/ml in the 600, 750 and 900 μg rHSA/IFNα2a groups and PEG-IFNα2a group, respectively. Conclusions The rHSA/IFNα2a treatment was well tolerated and can be administered biweekly. Similar efficacy in inhibiting HBV replication was observed in both PEG-IFNα2a and rHSA/IFNα2a 750 μg groups. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the tolerance, variability, and pharmacokinetics (PK) of QX001S, a biosimilar for ustekinumab, in healthy Chinese men. Methods: One hundred and seventy-eight healthy men were recruited in this randomized, double-blind, single-dose, two-arm, parallel study, and received 45 mg of QX001S or ustekinumab in a single subcutaneous injection. PK, immunogenicity, and tolerance were evaluated in all participants for a period of 113°days. Results: The similarity between the two drugs was determined by comparing the baseline characteristics for each drug. The PK parameters were similar in the two groups: QX001S (n = 89) and ustekinumab (n = 88). The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) of QX001S to the reference (ustekinumab) for the maximum observable serum concentration (C max ), area under the curve (AUC) from zero to the final quantifiable concentration (AUC0–t), and AUC from zero to infinity (AUC0–∞) were 100.90–118.68%, 98.71–115.26%, and 98.49–115.81%, respectively, which were within the predefined bioequivalence limit of 80.00–125.00%. High inter-subject variability (ranging from 32.0 to 33.5%) was observed. A total of 17 participants (19.1%) in the QX001S group and 36 (40.9%) in the ustekinumab group developed anti-drug antibodies (ADA) after administration. Nevertheless, the ADA did not affect the outcomes of the bioequivalence tests. Adverse reactions were recorded in 38 individuals injected with QX001S and 37 injected with ustekinumab. The most common adverse reactions were upper respiratory infection and elevated alanine aminotransferase. Conclusions: Our study ratified pharmacokinetic biosimilarity between QX001 S and ustekinumab, with high variability between subjects. [ABSTRACT FROM AUTHOR]