Impact of Dihydrocapsaicin on the Metabolism of Efavirenz In Vitro and In Vivo

Efavirenz (EFV) is the first-line treatment for acquired immunodeficiency syndrome. However, capsaicin may affect its properties, although the underlying mechanisms remain unknown. This study aimed to investigate the effects of dihydrocapsaicin (DHC) on the pharmacokinetics of EFV both in vivo and in vitro. Twelve Sprague-Dawley rats were divided into two groups including experimental and control. The experimental group was pretreated with DHC (10 mg/kg/day) for two weeks with 5% sodium carboxymethyl cellulose prior to receiving EFV. After a single-dose oral administration of 56 mg/kg EFV, blood samples (50 μL) were collected from the caudal vein and analyzed. The effects of DHC on EFV in vitro were further studied in rat liver microsomes (RLMs). The area under the plasma concentration-time curve for EFV increased from 8821.45 ± 2877.31 to 22347.15 ± 7579.96 μg/mL/h (p < 0.05); the maximum plasma time increased from 2.50 ± 0.84 to 3.50 ± 0.55 h (p < 0.05) and elimination half-life increased from 3.13 ± 0.87 to 3.51 ± 0.79 h (p < 0.05). In contrast, the plasma clearance rate decreased from 6.71 ± 2.48 to 2.65 ± 0.98 L/h/kg (p < 0.05) in the experimental group compared to that in the control group. Additionally, the results showed that DHC significantly inhibited the metabolism of EFV in RLMs. Drug-drug interactions were observed between DHC and EFV, altering the pharmacokinetics of EFV both in vivo and in vitro. The dosage of capsaicin should be monitored and adjusted in patients receiving EFV maintenance therapy.