Prediction of Maternal and Fetal Pharmacokinetics of Dolutegravir and Raltegravir Using Physiologically Based Pharmacokinetic Modeling

Xiaomei I Liu; Jeremiah D Momper; Natella Y Rakhmanina; Dionna J Green; Gilbert J Burckart; Tim R Cressey; Mark Mirochnick; Brookie M Best; John N van den Anker; André Dallmann

doi:10.1007/s40262-020-00897-9

Prediction of Maternal and Fetal Pharmacokinetics of Dolutegravir and Raltegravir Using Physiologically Based Pharmacokinetic Modeling

Clin Pharmacokinet. 2020 Nov;59(11):1433-1450. doi: 10.1007/s40262-020-00897-9.

Authors

Xiaomei I Liu¹, Jeremiah D Momper², Natella Y Rakhmanina^{3

4}, Dionna J Green⁵, Gilbert J Burckart⁶, Tim R Cressey^{7

8

9}, Mark Mirochnick¹⁰, Brookie M Best², John N van den Anker^{3

11}, André Dallmann^{11

12}

Affiliations

¹ Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA. [email protected].
² Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
³ Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA.
⁴ Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA.
⁵ Office of Pediatric Therapeutics, US Food and Drug Administration, Silver Spring, MD, USA.
⁶ Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, MD, USA.
⁷ PHPT/IRD 174, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
⁸ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁹ Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
¹⁰ Boston University, School of Medicine, Boston, MA, USA.
¹¹ Division of Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Basel, Switzerland.
¹² Clinical Pharmacometrics, Bayer, Leverkusen, Germany.

Abstract

Predicting drug pharmacokinetics in pregnant women including placental drug transfer remains challenging. This study aimed to develop and evaluate maternal-fetal physiologically based pharmacokinetic models for two antiretroviral drugs, dolutegravir and raltegravir.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Fetus / drug effects
HIV Infections* / drug therapy
HIV Integrase Inhibitors* / pharmacokinetics
HIV Integrase Inhibitors* / therapeutic use
Heterocyclic Compounds, 3-Ring / pharmacokinetics*
Heterocyclic Compounds, 3-Ring / therapeutic use
Humans
Maternal Exposure
Oxazines / pharmacokinetics*
Oxazines / therapeutic use
Piperazines / pharmacokinetics*
Piperazines / therapeutic use
Placenta
Pregnancy
Pyridones / pharmacokinetics*
Pyridones / therapeutic use
Raltegravir Potassium / pharmacokinetics*
Raltegravir Potassium / therapeutic use

Substances

HIV Integrase Inhibitors
Heterocyclic Compounds, 3-Ring
Oxazines
Piperazines
Pyridones
Raltegravir Potassium
dolutegravir

Abstract

Publication types

MeSH terms

Substances

Grants and funding