Hypercholesterolemia frequently occurs in patients treated with efavirenz who cannot be treated adequately with statins because of drug interactions. These patients may benefit from cholesterol-lowering therapy with ezetimibe. This study determined the influence of single-dose and multiple-dose efavirenz (400 mg/day for 9 days) on the pharmacokinetics and sterol-lowering of ezetimibe (10 mg) in 12 healthy subjects. In addition, the influence of efavirenz on genome-wide intestinal expression and in vitro function of ABCB1, ABCC2, UGT1A1, and OATP1B1 was studied. Efavirenz (multiple dose) had no influence on the pharmacokinetics and lipid-lowering functions of ezetimibe. Intestinal expression of enzymes and transporters (e.g., ABCB1, ABCC2, and UGT1A1) was not affected by chronic efavirenz. Efavirenz (single dose) slightly increased ezetimibe absorption and markedly decreased exposure to ezetimibe-glucuronide (single dose and multiple dose), which may be explained by inhibition of UGT1A1 and ABCB1 (in vitro data). Ezetimibe had no effect on the disposition of efavirenz. Consequently, ezetimibe may be a safe and efficient therapeutic option in patients with HIV infection.

Immunosuppressive therapy is frequently associated with hypercholesterolemia, calling for lipid-lowering treatment without adverse drug interactions. One option is treatment with the cholesterol absorption inhibitor ezetimibe. We have shown in vitro that ezetimibe and tacrolimus may interact in competition for intestinal UGT1A1 and ABCB1 at concentrations reached in gut lumen after oral administration. However, this clinical study in healthy volunteers showed that the expected pharmacokinetic interaction between ezetimibe and tacrolimus is not of clinical relevance.

In this retrospective study, analyzing blood samples from daily clinical practice of patients in various clinical settings and with different indications for antifungal therapy, concomitant medication of lorazepam was associated with decreased posaconazole concentrations. Therefore, lorazepam but not temazepam might induce posaconazole clearance by glucuronidation.