A total of 32 patients and healthy subjects were evaluated in this open-label, two-part study. Pharmacokinetic parameters after a single oral dose of
aprepitant 240 mg were measured in eight patients with
end-stage renal disease (
ESRD) requiring haemodialysis, eight patients with severe
renal insufficiency (SRI [24-hour
creatinine clearance <30 mL/min/1.73 m(2)]) and 16 healthy and age-, sex- and weight-matched subjects (controls).
RESULTS: In
ESRD patients, the area under the plasma concentration-time curve (AUC) from 0 to 48 hours (AUC(48)) for
aprepitant was on average approximately 36% lower than that observed in control subjects (ratio [
ESRD patients/healthy controls] of geometric means = 0.64), but the 90% confidence interval 0.52, 0.78 for the ratio of true mean AUC(48) fell within the predefined target interval of 0.5, 2.0. Also in
ESRD patients, there was no statistically or clinically significant difference in unbound
aprepitant AUC (which may be more clinically relevant than total
aprepitant AUC) when compared with healthy control subjects.
Aprepitant pharmacokinetic parameters in
ESRD patients were clinically similar when haemodialysis was initiated at 4 hours or 48 hours after
aprepitant administration. In SRI patients, the ratio (SRI patients/healthy controls) of
aprepitant AUC from zero to infinity (AUC(infinity)) geometric mean value was 0.79 with a 90% confidence interval of 0.56, 1.10. On average, in SRI patients the principal
aprepitant pharmacokinetic parameters (AUC(infinity), initial maximum plasma concentration [C(max)], time to initial C(max), and apparent elimination half-life) were not statistically different from those obtained in healthy control subjects.
Aprepitant was generally well tolerated in both
ESRD and SRI patients.
CONCLUSION: The results of this study demonstrate that
ESRD, haemodialysis and SRI have no clinically meaningful effect on
aprepitant pharmacokinetics. Therefore, no dosage adjustment of
aprepitant is warranted in SRI or
ESRD patients.