Primaquine Pharmacokinetics in Lactating Women and Their Infants
Status:
Completed
Trial end date:
2014-12-01
Target enrollment:
Participant gender:
Summary
The weight of malaria falls most heavily on young children and pregnant women but studies of
the safety of antimalarials in pregnancy and lactation are few. The only recommended
medication used for radical treatment of P.vivax is primaquine. The 2010 WHO malaria
guidelines recommend its use in all patients with P.vivax infection in areas of low
transmission, in the absence of contraindications. Primaquine is contraindicated in
pregnancy. The postpartum period presents a key opportunity to definitively treat women who
suffer multiple malaria relapses during pregnancy. The 2010 WHO malaria treatment guidelines
allow for primaquine use during lactation but there are no studies to date quantifying
primaquine excretion in breast milk and the dose that breastfed infants would be exposed to
is unknown. The investigators propose to study the pharmacokinetics of primaquine in maternal
and infant plasma and in breast milk during a 14 day radical treatment of P.vivax.
Some inferences about the expected behavior of primaquine in lactation can be drawn from its
known pharmacologic properties. Primaquine pharmacokinetics have been well characterized in
healthy subjects and malaria patients after single and multiple oral dosing. Peak
concentrations are reached within 2-3 hours after dosing and the plasma elimination half-life
is ~7 hours. It is extensively distributed in the tissue and largely metabolized to inert
carboxyprimaquine, the major plasma metabolite, which undergoes further biotransformation to
unknown metabolites that are probably more toxic than the parent compound. The identification
of other metabolites in humans has been difficult to pursue because the expected aminophenol
metabolites are unstable.
No pharmacokinetic studies have been done to measure primaquine excretion in breast milk. A
few studies have been done of other antimalarials during lactation and have shown low levels
of drug in breast milk during treatment.