Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Itacitinib is a novel, selective, Janus kinase 1 inhibitor in development for treatment of graft-versus-host disease. The objective of this study was to assess pharmacokinetics and safety of 300-mg itacitinib dosed in participants with normal renal function (n = 10), severe renal impairment (n = 8), and end-stage renal disease (ESRD) on hemodialysis (n = 8). Serial plasma and urine samples (urine from normal and severe groups only) were collected before dosing until 72 hours after dosing. In the ESRD group, itacitinib was evaluated in 2 periods, when dosed before (period 1) and after (period 2) a hemodialysis session. Geometric mean ratios (90% confidence interval) in participants with severe renal impairment, ESRD period 1 and ESRD period 2 relative to participants with normal renal function were 1.65 (1.13-2.39), 0.71 (0.49-1.03), and 0.83 (0.57-1.20) for maximum plasma drug concentration and 2.23 (1.56-3.18), 0.81 (0.57-1.16), and 0.95 (0.66-1.35) for area under the plasma concentration-time curve from time zero to infinity. Itacitinib was well tolerated, and 3 grade 1 treatment-emergent adverse events were reported over the course of the study. Given the magnitude of exposure changes in participants with severe renal impairment or ESRD and the historic risk-benefit profile, no dose adjustment is recommended for itacitinib in patients with impaired renal function, although the final dosage recommendation will be based on cumulative pharmacokinetics and safety from this study and from the pivotal graft-versus-host disease trial. Additionally, itacitinib may be administered to patients undergoing dialysis regardless of the time of dialysis.
Pubmed ID: 32149388
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A second-generation retrovirus producer lines for the generation of helper free ecotropic and amphotropic retroviruses. The lines are based on the 293T cell line (a human embryonic kidney line transformed with adenovirus E1a and carrying a temperature sensitive T antigen co-selected with neomycin). The unique feature of this cell line is that it is highly transfectable with either calcium phosphate mediated transfection or lipid-based transfection protocols-- up to 50% or higher of cells can be transiently transfected. The lines were created by placing into 293T cells constructs capable of producing gag-pol, and envelope protein for ecotropic and amphotropic viruses. The lines offered advantages over previous stable systems in that virus can be produced in just a few days. Academic and non-profit laboratories may obtain the Phoenix cells from either Allele Biotechnology or the National Gene Vector Bank. The vectors may be obtained from Addgene. They are no longer distributing these reagents from the lab.
View all literature mentions