2.8 Predictions of the pharmacokinetics of LAI CAB and LAI RPV in pregnancy
The two approved dosage regimens for LAI CAB comprise of 600 mg CAB administered intramuscularly followed by 400 mg IM CAB every month (LAI CAB monthly dosing of CAB) or 600 mg IM CAB every 2 months (LAI CAB bimonthly dosing). Like CAB, approved dosage regimens for LAI RPV include 900 mg IM RPV for one month followed by 600 mg IM RPV every month (LAI RPV monthly dosing of RPV) or 900 mg IM RPV every 2 months (LAI RPV bimonthly dosing). In all the cases, the administration of the LAI doses is preceded by their respective oral lead-in doses for one month.
Simulations were performed to predict the disposition of both the monthly and bimonthly LAI CAB and LAI RPV for a total period of 12 weeks (i.e. 3 months) without the oral lead-in components. Results from a recent study suggest comparable plasma trough concentrations (Ctrough) after the first LAI dose with or without an oral lead-in though the study reported data for only CAB [53]. The simulations in pregnancy PBPK model were initiated at first (week 1-13), second (week 14-26), and third (week 28-40) trimesters of pregnancy. In addition, the female adult PBPK model was used to run similar simulations for a non-pregnant adult female. The simulations were performed to explore any differences in the disposition of both drugs if they were initiated in the first, second or third trimesters of pregnancy as compared to non-pregnant women. Predicted Ctrough were also compared against clinical target concentrations for RPV and CAB.