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Mefloquine transfer during in vitro human placenta perfusion
M M Barzago1, D Omarini, A Bortolotti
1Laboratory for Mother and Child Health, Istituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy.
Summary
Mefloquine (MQ) effectively treats malaria but its placental transfer is unclear. This study shows MQ crosses the placenta, reaching a steady state after 120 minutes, supporting its use in pregnant women.
Area of Science:
- Pharmacology
- Maternal-Fetal Medicine
- Infectious Diseases
Background:
- Mefloquine (MQ) is a key antimalarial drug for chloroquine-resistant Plasmodium falciparum.
- Limited data exists on Mefloquine's transplacental transfer and kinetics in humans.
Purpose of the Study:
- To investigate the transplacental transfer and pharmacokinetic profile of Mefloquine in a human placental perfusion model.
- To determine the time course and extent of Mefloquine transfer from maternal to fetal circulation.
Main Methods:
- Human placental perfusion model using recirculating maternal and fetal circuits for 180 minutes.
- Validation of placental viability through gas exchange and metabolic measurements (glucose, lactate).
- Comparison of Mefloquine kinetics with antipyrine, a standard placental transfer marker.
Main Results:
- Mefloquine exhibited biexponential disappearance from maternal circulation, indicating rapid placental tissue distribution.
- The fetomaternal mass ratio stabilized after 120 minutes, reaching 0.46 ± 0.07.
- Equilibrium concentrations across the placenta were estimated at 178 ± 31 minutes, with a clearance of 3.36 ± 0.38 ml/min.
- Approximately 40% of the maternal Mefloquine dose was found in placental tissue, and 11% transferred to the fetal circulation.
Conclusions:
- Mefloquine demonstrates significant transfer across the human placenta.
- The pharmacokinetic profile supports the potential use of Mefloquine for malaria treatment and prophylaxis in pregnant women.
- Further comparative studies with other antimalarials are warranted.