OA-92 Clinically relevant enantiomer specific R- and S-praziquantel pharmacokinetic drug-drug interactions with efavirenz and ritonavir: implications for HIV and schistosomiasis co-infection

BackgroundHIV and schistosomiasis are the most widespread infections worldwide. The two diseases share the same epidemiological space, especially in poor regions where endemicity is high. Co-infections are therefore common. We conducted a clinical study to determine the effect of efavirenz and ritonavir on the pharmacokinetics of R- and S-praziquantel (PZQ) in healthy male participants. The aim was to increase knowledge towards the safe and efficacious use of PZQ especially in cases of coinfection and mass drug treatment programs where HIV status and concomitant drug intake is not considered prior to administration. MethodsWe conducted a non-randomized, open-label, single-dose, one sequence crossover study with 2 arms. A single oral dose of 40 mg/kg PZQ followed by a daily oral dose of either 400 mg efavirenz or 100 mg ritonavir was given to participants for 14 consecutive days. On day 14, they ingested a single 40 mg/kg dose of PZQ. We measured plasma levels up to 12 h on day 1 and day 14. Samples were analyzed by LC-MS. Pharmacokinetic analysis was conducted in WinNonlin to determine the primary endpoints (plasma T1/2, Cmin, and AUC). ResultsEfavirenz had a significant effect on the pharmacokinetics of PZQ (p < .05), reducing the AUC by 4-fold (1213.15 vs. 281.35 h·ng/ml for R-PZQ and 5669 vs. 871.84 h·ng/ml for S-PZQ). Ritonavir had no significant effect on R-PZQ but increased the AUC 2-fold for S-PZQ (p < .05) (4154.79 vs. 7291.05 h·ng/ml). ConclusionOur study showed clinically significant drug-drug interactions involving PZQ and efavirenz that should be considered in the treatment of schistosomiasis in regions where efavirenz-based ART is common. Using PZQ in HIV patients needs investigation, as there is a risk of both treatment failure and adverse effects because of induction and inhibition. Strategies to avoid these detrimental DDI should therefore be explored.