Boosted darunavir 800/100 mg twice daily might overcome interaction with rifampicin
29 June 2018. Related: Conference reports, PK and drug interactions, TB coinfection, PK Workshop 19th 2018 Baltimore.
Modelling study suggests darunavir/ritonavir twice 800/100 mg daily might be sufficient to overcome the interaction with rifampicin in HIV positive people co-infected with TB, according to data presented at the 19th International Workshop on Clinical Pharmacology.
Co-administration of rifampicin (RIF) and boosted darunavir (DRV) is contra-indicated due to significant pharmacokinetic (PK) interactions that can reduce the efficacy of DRV.
This study aimed to look at the effects of RIF on the PK of ritonavir (RTV)-boosted DRV (DRV/r) and strategies to overcome the interaction.
The investigators implemented in vitro results in physiologically-based pharmacokinetic (PBPK) models to identify DRV regimens with the highest likelihood of successful clinical outcomes.
In vitro inhibition studies confirmed the potent inhibition of RTV of the metabolism of DRV (IC50 RTV: 14 nM), which was counteracted by the induction observed following RIF treatment (IC50 RTV: 46 nM).
Simulated DRV/r PK parameters accurately predicted values previously seen in clinical studies for DRV Cmax, AUC24h, and Ctrough of DRV/r 800/100 mg once daily.
Addition of 600 mg RIF resulted in a significant decrease of DRV Cmax, AUC24h, and Ctrough in the various simulated regimens: DRV/r 800/100 mg once daily, 1600/200 mg once daily DRV/r and 800/100 mg twice daily.
The study generated a framework of in vitro data aimed at supporting the development of accurate PBPK models for predicting the PK of DRV/r as well as to predict potential drug-drug interaction following co-administration of RIF.
Based on these findings, the investigators suggested changing the DRV/r regimen from 800/100 mg once daily to 800/100 mg twice daily as the most promising regimen to counter the interaction of RIF 600 mg once daily in HIV positive people co-infected with TB.
Reference
Jacobs S et al. Predicted pharmacokinetic interactions of rifampicin with ritonavir-boosted darunavir. 19th International Workshop on Clinical Pharmacology. Poster abstract 37.