No abstract

Aims: A randomized, open-label, two-period, two-sequence crossover study was carried out for evaluating the bioequivalence of test (T) and reference (R) formulation of gefitinib in healthy Chinese volunteers. Methods: A total of eighty subjects were enrolled and randomized into two sequence groups. All subjects were orally administered of T or R formulation at dose of 250 mg. The plasma samples were obtained at before and after administration until post-dose 168 hour, and the drug concentrations were analyzed using validated high-performance liquid chromatography-tandem mass spectrometry method. Results: The 90% confidence interval of the geometric mean ratios were all within the range of 0.80-1.25 under fasting and fed conditions. As for the safety of both formulations, no serious or unexpected adverse events occurred during the study. Conclusions: Overall, the T formulation was bioequivalent with R formulation under fasting and fed conditions.

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1/L1 therapy and anti-CTLA-4 therapy, are associated with a unique spectrum of immune-related adverse events (irAEs). The association and clinical features of ICIs-related biliary disorders are not well characterized. Methods: Data were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Bile duct and gallbladder diseases were defined by the Medical Dictionary for Regulatory Activities (MedDRA). We performed disproportionality analysis using reporting odds ratios (ROR) and information component (IC). The result was defined as a signal if the lower limit of the 95% confidence interval for ROR is over 1 and the number of cases ≥5, or the lower limit of 95% confidence interval for the IC (IC025)>0. Results: 906 reports of ICI-related bile duct and gallbladder events were identified. The mean age was 64.8±12.1 years and the AEs occurred more in men (60.1% vs 39.9%). ICIs were associated with increased reporting of bile duct diseases (ROR 3.35, 95%CI 3.07-3.66; IC0251.41), especially cholangitis (ROR 5.52, 95% CI 4.94-6.17; IC0251.93); while we didn’t identify signal of gallbladder disease (ROR 0.96, 95%CI 0.86-1.08; IC025 -0.22). PD-1/L1 inhibitors and combination regimen were associated with a spectrum of distinct classes of bile duct disease while anti-CTLA-4 therapy (ipilimumab) had no association with any bile duct and gallbladder diseases. Conclusions: PD-1/L1 inhibitors showed increased reporting of cholangiopathy, especially for cholangitis. Physicians should be aware of this potential adverse event.