Co-administration of rilpivirine and rifampin is expected to cause a profound decrease in concentration of rilpivirine. Therefore, the co-administration of rilpivirine and rifampin should be avoided or a different ARV should be recommended in place of rilpivirine.
Rilpivirine vs rifampin
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Study Design
The PBPK model was designed in Simbiology v. 4.3.1 (MATLAB 2013b) and 100 healthy adult individuals were used for simulations. PBPK models were qualified for the three drugs against available oral clinical data. Standard oral doses of25 mg and 600 mg were used for rilpivirine (RPV) and rifampin (RIF), respectively. Loading doses of 900 mg were used for RPV, and 600/900 mg were used as q4/8-weekly IM maintenance doses for RPV. Models were also qualified against PK data in the LATTE-2 IM cabotegravir (CAB) and RPV study. Oral midazolam (CYP3A4 probe)- RIF and RPV-RIF drug-drug interaction (DDI) models were also qualified against PK data from clinical studies. The PBPK models were assumed to be qualified if the simulated values were ± 100 % from the mean reported clinical values. Authors evaluated the effect of 600 mg oral once-daily RIF on the PK of long acting Intramuscular (LA IM) and RPV loading and maintenance doses. Variation in PK parameters AUC, Cmax and Ctrough values are reported.
Study Results
A marked reduction was observed for rilpivirine PK, with a decrease in Cmax, AUC and Ctrough of 90.9%, 83.9% and 83.6% for the loading dose, and a reduction in these parameters between 80.5% and 83% for maintenance doses.
Study Conclusions
Models were qualified and PK data successfully predicted for RPV with RIF. This computational approach supports the prediction of potential DDIs for LA regimens, which cannot be readily investigated in vivo due to ethical and logistical barriers. This approach could rationally guide the design of alternative dosing strategies. The co-administration of RIF with RPV is predicted to substantially decrease ARV concentrations.
References
Rajoli RKR, Curley P, Back D, Flexner CW, Owen A, Siccardi M. In silico drug interaction of long-acting rilpivirine and cabotegravir with rifampin. Conference On Retroviruses And Opportunistic Infections. Boston, MA, USA. ; March 2018.
Rilpivirine vs rifampin
^
Study Design
The PBPK model was designed in Simbiology v. 4.3.1 (MATLAB 2013b) and 100 healthy adult individuals were used for simulations. PBPK models were qualified for the three drugs against available oral clinical data. Standard oral doses of25 mg and 600 mg were used for rilpivirine (RPV) and rifampin (RIF), respectively. Loading doses of 900 mg were used for RPV, and 600/900 mg were used as q4/8-weekly IM maintenance doses for RPV. Models were also qualified against PK data in the LATTE-2 IM cabotegravir (CAB) and RPV study. Oral midazolam (CYP3A4 probe)- RIF and RPV-RIF drug-drug interaction (DDI) models were also qualified against PK data from clinical studies. The PBPK models were assumed to be qualified if the simulated values were ± 100 % from the mean reported clinical values. Authors evaluated the effect of 600 mg oral once-daily RIF on the PK of long acting Intramuscular (LA IM) and RPV loading and maintenance doses. Variation in PK parameters AUC, Cmax and Ctrough values are reported.
Study Results
A marked reduction was observed for rilpivirine PK, with a decrease in Cmax, AUC and Ctrough of 90.9%, 83.9% and 83.6% for the loading dose, and a reduction in these parameters between 80.5% and 83% for maintenance doses.
Study Conclusions
Models were qualified and PK data successfully predicted for RPV with RIF. This computational approach supports the prediction of potential DDIs for LA regimens, which cannot be readily investigated in vivo due to ethical and logistical barriers. This approach could rationally guide the design of alternative dosing strategies. The co-administration of RIF with RPV is predicted to substantially decrease ARV concentrations.
References
Rajoli RKR, Curley P, Back D, Flexner CW, Owen A, Siccardi M. In silico drug interaction of long-acting rilpivirine and cabotegravir with rifampin. Conference On Retroviruses And Opportunistic Infections. Boston, MA, USA. ; March 2018.
Rilpivirine vs rifampin
^
Study Design
The PBPK model was designed in Simbiology v. 4.3.1 (MATLAB 2013b) and 100 healthy adult individuals were used for simulations. PBPK models were qualified for the three drugs against available oral clinical data. Standard oral doses of25 mg and 600 mg were used for rilpivirine (RPV) and rifampin (RIF), respectively. Loading doses of 900 mg were used for RPV, and 600/900 mg were used as q4/8-weekly IM maintenance doses for RPV. Models were also qualified against PK data in the LATTE-2 IM cabotegravir (CAB) and RPV study. Oral midazolam (CYP3A4 probe)- RIF and RPV-RIF drug-drug interaction (DDI) models were also qualified against PK data from clinical studies. The PBPK models were assumed to be qualified if the simulated values were ± 100 % from the mean reported clinical values. Authors evaluated the effect of 600 mg oral once-daily RIF on the PK of long acting Intramuscular (LA IM) and RPV loading and maintenance doses. Variation in PK parameters AUC, Cmax and Ctrough values are reported.
Study Results
A marked reduction was observed for rilpivirine PK, with a decrease in Cmax, AUC and Ctrough of 90.9%, 83.9% and 83.6% for the loading dose, and a reduction in these parameters between 80.5% and 83% for maintenance doses.
Study Conclusions
Models were qualified and PK data successfully predicted for RPV with RIF. This computational approach supports the prediction of potential DDIs for LA regimens, which cannot be readily investigated in vivo due to ethical and logistical barriers. This approach could rationally guide the design of alternative dosing strategies. The co-administration of RIF with RPV is predicted to substantially decrease ARV concentrations.
References
Rajoli, KRK, Curley, P, Back, D, Flexner, CW, Owen, A. In silico drug interaction of long-acting rilpivirine and cabotegravir with rifampin. Conference On Retroviruses And Opportunistic Infections. Boston. ; March 2018.
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