Updated pharmacokinetic considerations for the use of antimalarial drugs in pregnant women

ABSTRACT

Introduction

The association between pregnancy and altered drug pharmacokinetic (PK) properties is acknowledged, as is its impact on drug plasma concentrations and thus therapeutic efficacy. However, there have been few robust PK studies of antimalarial use in pregnancy. Given that inadequate dosing for prevention or treatment of malaria in pregnancy can result in negative maternal/infant outcomes, along with the potential to select for parasite drug resistance, it is imperative that reliable pregnancy-specific dosing recommendations are established.

Areas covered

PK studies of antimalarial drugs in pregnancy. The present review summarizes the efficacy and PK properties of WHO-recommended therapies used in pregnancy, with a focus on PK studies published since 2014.

Expert opinion

Changes in antimalarial drug disposition in pregnancy are well described, yet pregnant women continue to receive treatment regimens optimized for non-pregnant adults. Contemporary in silico modeling has recently identified a series of alternative dosing regimens that are predicted to provide optimal therapeutic efficacy for pregnant women.

KEYWORDS:

• Artemether-lumefantrine
• dihydroartemisinin-piperaquine
• dose modification
• intermittent preventive treatment in pregnancy (IPTp)
• malaria
• mefloquine
• pharmacokinetics
• pregnancy
• sulfadoxine-pyrimethamine

Article highlights

• Physiologic changes occur during pregnancy that result in dynamic and profound alterations in drug pharmacokinetics, which can potentially influence both drug efficacy and safety.

• Most conventional antimalarial treatment regimens in pregnancy are guided by dose optimization for non-pregnant adults.

• Pharmacokinetic modelling demonstrates that an extended treatment regimen of artemether-lumefantrine (5 days versus 3 days) provides pregnant women with an equivalent total lumefantrine drug exposure compared to non-pregnant controls.

• Simulations of dihydroartemisinin-piperaquine as a candidate for IPTp predict significantly improved piperaquine drug exposure and prophylactic efficacy, and reduced peak concentrations (thus limiting adverse events) in pregnant women given daily low doses compared to monthly full dose.

• Drug interactions, particularly those between antimalarial and antiretroviral therapies, need to be comprehensively investigated to ensure safety and adequate drug exposure for both treatments.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.