Intrapatient and Interpatient Pharmacokinetic Variability of Raltegravir in the Clinical Setting

Raltegravir (RAL) is the first in class integrase inhibitor and is licensed for administration at 400 mg twice daily. RAL pharmacokinetics are characterized by high interpatient variability and recently RAL plasma exposure has been correlated with efficacy. RAL is primarily metabolized by glucuronidation via uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and UGT1A128 considered to be the main genetic variant associated with decreased UGT1A1 expression. This study investigated variability in RAL trough plasma concentrations (Ctrough) in the clinical setting, the effect of UGT1A128 and concomitant antiretrovirals.