In this article, we will discuss Erdafitinib (Pharmacokinetics). So, let’s get started.
Following administration of 8 mg once daily, the mean (coefficient of variation
[CV%]) erdafitinib steady-state maximum observed plasma concentration (Cmax),
area under the curve (AUCtau), and minimum observed plasma concentration (Cmin) were 1,399 ng/mL (51%), 29,268 ng•h/mL (60%), and 936 ng/mL (65%), respectively. Following single and repeat once daily dosing, erdafitinib exposure (maximum observed plasma concentration [Cmax] and area under the plasma concentration time curve [AUC]) increased proportionally across the dose range of 0.5 to 12 mg (0.06 to 1.3 times the maximum approved recommended dose). Steady state was achieved after 2 weeks with once daily dosing and the mean accumulation ratio was 4-fold.
Median time to achieve peak plasma concentration (tmax) was 2.5 hours (range: 2
to 6 hours).
Effect of Food
No clinically meaningful differences with erdafitinib pharmacokinetics were
observed following administration of a high-fat and high-calorie meal (800 calories
to 1,000 calories with approximately 50% of total caloric content of the meal from
fat) in healthy subjects.
The mean apparent volume of distribution of erdafitinib was 29 L in patients. Erdafitinib protein binding was 99.8% in patients, primarily to alpha-1-acid glycoprotein.
The mean total apparent clearance (CL/F) of erdafitinib was 0.362 L/h in patients. The mean effective half-life of erdafitinib was 59 hours in patients.
Erdafitinib is primarily metabolized by CYP2C9 and CYP3A4. The contribution of CYP2C9 and CYP3A4 in the total clearance of erdafitinib is estimated to be 39% and 20% respectively. Unchanged erdafitinib was the major drug-related moiety in plasma, there were no circulating metabolites.
Following a single oral dose of radiolabeled erdafitinib, approximately 69% of the dose was recovered in feces (19% as unchanged) and 19% in urine (13% as unchanged).