MEFLOQUINE TRANSFER DURING IN-VITRO HUMAN PLACENTA PERFUSION

Mefloquine (MQ) is highly effective in the treatment and prophylaxis o f chloroquine-resistant Plasmodium falciparum malaria. Despite its wid espread use, scant information is available on the transplacental prof ile and time course of MQ transfer across the human placenta. Six huma n placentas were perfused with human plasma for 180 min using recircul ating maternal and fetal circuits. The viability of the placental prep aration was validated measuring oxygen and carbon dioxide balance and the rates of glucose consumption and lactate production. MQ data were compared with antipyrine, a routine marker in placental perfusions. Di sappearance of MQ from the maternal circulation after a dose of 0.8 mg /liter was biexponential, with a first, rapid distribution phase into the placental tissue. The apparent first-order distribution (lambda(1) ) and elimination (lambda(z)) rate constants were 0.043 +/- 0.014 min( -1) and 0.020 +/- 0.007 min(-1), respectively. The fetomaternal mass r atio became constant (0.46 +/- 0.07) after 120 min of perfusion and th e time needed to achieve equal concentrations on both sides of the pla centa was 178 +/- 31 min. MQ clearance was 3.36 +/- 0.38 ml/min. About 40% of the MQ maternal dose was recovered in tissue and 11% appeared in the fetal circulation. These data provide support for using MQ in p regnant women for both the treatment and prophylaxis of Plasmodium mal aria, although comparison with other compounds are needed.