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To assess the pharmacokinetics (PK) of raltegravir and ezetimibe when co-administered to healthy volunteers.This was a prospective, open-label, crossover study, with subjects randomly assigned to group 1 (raltegravir 400 mg twice daily, raltegravir plus ezetimibe 10 mg once daily, wash-out period, ezetimibe) or group 2 (ezetimibe, raltegravir plus ezetimibe, wash-out period, raltegravir); all phases lasted for 10 days. Steady-state full PK sampling was performed at days 10, 20 and 40. Raltegravir and ezetimibe PK parameters were determined by non-compartmental methods and comparisons in the presence of the potentially interactive drug measured by geometric mean ratio (GMR) and 95% confidence intervals (CIs).Twenty subjects (10 females) completed the study. Raltegravir PK parameters did not change significantly in the presence of ezetimibe: GMRs (95% CI) were 1.16 (0.89–1.51) for AUC0–12, 1.13 (0.81–1.58) for maximum plasma concentration (Cmax) and 1.12 (0.72–1.74) for trough concentration (Ctrough). Ezetimibe AUC0–24 and Ctrough were lower in the presence of raltegravir [GMRs (95% CI) were 0.79 (0.68–0.91) for AUC0–24 and 0.78 (0.60–0.99) for Ctrough], while ezetimibe glucuronide Cmax was 40% higher (90% CI 1.17–1.66). There was marked inter-individual variability in the PK of the two drugs, especially during co-administration.There were no significant changes in raltegravir PK parameters with or without ezetimibe. However, in the presence of raltegravir, ezetimibe AUC0–24 and Ctrough were significantly lower (>20%) and ezetimibe glucuronide Cmax was higher. Clinical data to assess the importance of the change in ezetimibe concentrations are warranted.