Primaquine Pharmacokinetics in Lactating Women and Their Infants

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Oxford
• Treatments: Primaquine

Criteria

Inclusion Criteria:

• Lactating women aged 18 years and older who are breast feeding one infant aged more than 28 days.

• G6PD normal

• History of proven P.vivax malaria that has not been treated with primaquine

• Willingness and ability to comply with the study protocol for the duration of the trial

• Written informed consent provided

Exclusion Criteria:

• Known hypersensitivity to primaquine, defined as history of erythroderma/other severe cutaneous reaction, angioedema or anaphylaxis

• Glucose-6-phosphate-dehydrogenase (G6PD) deficiency in mother

• Glucose-6-phosphate-dehydrogenase (G6PD) deficiency in infant

• Pregnancy (urine test for HCG to be performed on any woman of child bearing age unless menstruating)

• Blood smear positive for malaria at the time of enrolment

• Presence of intercurrent illness or any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study

• Hematocrit (HCT) <25% in the mother or <33% in the infant

• Use of medications other than antipyretics in the past 7 days or Chloroquine in the past 2 months.

• Use of primaquine since most recent malaria episode.