title: Mefloquine transfer during in vitro human placenta perfusion.
abstract: Mefloquine (MQ) is highly effective in the treatment and prophylaxis of chloroquine-resistant Plasmodium falciparum malaria. Despite its widespread use, scant information is available on the transplacental profile and time course of MQ transfer across the human placenta. Six human placentas were perfused with human plasma for 180 min using recirculating maternal and fetal circuits. The viability of the placental preparation 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. Disappearance 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 ratio became constant (0.46 +/- 0.07) after 120 min of perfusion and the time needed to achieve equal concentrations on both sides of the placenta 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 pregnant women for both the treatment and prophylaxis of Plasmodium malaria, although comparison with other compounds are needed.
authors.affiliation: Laboratory for Mother and Child Health, Istituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy.
authors.forename: M M
authors.initials: MM
authors.lastname: Barzago
authors.forename: D
authors.initials: D
authors.lastname: Omarini
authors.forename: A
authors.initials: A
authors.lastname: Bortolotti
authors.forename: F F
authors.initials: FF
authors.lastname: Stellari
authors.forename: G
authors.initials: G
authors.lastname: Lucchini
authors.forename: S
authors.initials: S
authors.lastname: Efrati
authors.forename: M
authors.initials: M
authors.lastname: Bonati
mesh_terms: D000983:Antipyrine / Q000493:pharmacokinetics; D001692:Biological Transport; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008431:Maternal-Fetal Exchange; D015767:Mefloquine / Q000493:pharmacokinetics*; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D007773:Lactates; D019344:Lactic Acid; D005947:Glucose; D010100:Oxygen; D000983:Antipyrine; D015767:Mefloquine