Pharmacokinetics of Efavirenz 600 mg Once Daily During Pregnancy and Post Partum in Ghanaian Women Living With HIV

Lartey, Margaret; Kenu, Ernest; Lassey, A.T.; Ntumy, Michael; Ganu, Vincent; Sam, Miriam; Boamah, Isaac; Gilani, Fizza S.; Yang, Hongmei; Burch, Gena M.; Norman, Jennifer; Peloquin, Charles A.; Kwara, Awewura

doi:10.1016/j.clinthera.2020.07.008

Cited by 5 publications

(4 citation statements)

References 13 publications

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“…Data for Cressey et al, 40 Kreitchmann et al, 41 and Olagunju et al 37 are expressed as median and those for Lamorde et al 42 and Lartey et al 43 are expressed as geometric mean values.…”

Section: Resultsmentioning

confidence: 99%

“…Using the final PBPK model for efavirenz, plasma concentration-time profiles were simulated at different stages of pregnancy and compared to clinically observed data from 5 clinical studies. 37,[40][41][42][43] The posology used in these studies is listed together with further details in Table 2. Pharmacokinetic simulations were conducted in virtual populations of 500 pregnant individuals.…”

Section: Evaluation Of the Pregnancy Pbpk Model For Efavirenzmentioning

confidence: 99%

“…The thick solid line represents the simulated geometric mean (for Lamorde et al42 ) or median (all other studies), and the shaded area represents the simulated 5th-95th percentile range; the circles represent the observed geometric mean (for Lamorde et al42 ) or median (all other studies); error bars represent the observed geometric standard deviation (for Lamorde et al42 ) or interquartile range (for Olagunju et al37 ). Observed data were all taken from the literature 37,[40][41][42][43]. conc, concentration.…”

mentioning

confidence: 99%

“…Simulated and Observed Pharmacokinetic Parameters for Efavirenz in Pregnant Women AUC τ ,ss , area under the plasma concentration-time curve over the dosing interval in steady state; C max,ss , maximum plasma concentration in steady state; C 24h,ss , plasma concentration at 24 hours after last dose administration in steady state; NA, not available; t max , time at which maximum plasma concentration in steady state occurs. Data for Cressey et al,40 Kreitchmann et al,41 and Olagunju et al37 are expressed as median and those for Lamorde et al42 and Lartey et al43 are expressed as geometric mean values.…”

mentioning

confidence: 99%

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Mechanistic Modeling of the Drug‐Drug Interaction Between Efavirenz and Dolutegravir: Is This Interaction Clinically Relevant When Switching From Efavirenz to Dolutegravir During Pregnancy?

Dallmann

Anker

Ahmadzia

et al. 2023

The Journal of Clinical Pharma

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Following the 2021 World Health Organization's updated recommendations on the management of HIV infection, millions of people living with HIV are currently switched from efavirenz‐based antiretroviral therapy to dolutegravir‐based antiretroviral therapy. Pregnant individuals transitioning from efavirenz to dolutegravir might be at increased risk of insufficient viral suppression in the immediate postswitch period because both efavirenz‐ and pregnancy‐related increases in hormone levels induce enzymes involved in dolutegravir metabolism, namely, cytochrome P450 3A4 and uridine 5′‐diphospho‐glucuronosyltransferase 1A1. This study aimed at developing physiologically based pharmacokinetic models to simulate the switch from efavirenz to dolutegravir in the late second and third trimester. To this end, the drug‐drug interaction between efavirenz and the uridine 5′‐diphospho‐glucuronosyltransferase 1A1 substrates dolutegravir and raltegravir was first simulated in nonpregnant subjects. After successful validation, the physiologically based pharmacokinetic models were translated to pregnancy and dolutegravir pharmacokinetics following efavirenz discontinuation were predicted. Modeling results indicated that, at the end of the second trimester, both efavirenz concentrations and dolutegravir trough concentrations fell below respective pharmacokinetic target thresholds (defined as reported thresholds producing 90%‐95% of the maximum effect) during the time interval from 9.75 to 11 days after dolutegravir initiation. At the end of the third trimester, this time interval spanned from 10.3 days to >4 weeks after dolutegravir initiation. These findings suggest that dolutegravir exposure in the immediate post‐efavirenz switch period during pregnancy may be suboptimal, leading to HIV viremia and, potentially, resistance. The clinical implications of these findings remain to be substantiated by future studies.

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“…Data for Cressey et al, 40 Kreitchmann et al, 41 and Olagunju et al 37 are expressed as median and those for Lamorde et al 42 and Lartey et al 43 are expressed as geometric mean values.…”

Section: Resultsmentioning

confidence: 99%