A Pilot Study of the Maternal‐Fetal Pharmacokinetics of Furosemide in Plasma, Urine, and Amniotic Fluid of Hypertensive Parturient Women Under Cesarean Section

Abstract

The third trimester of pregnancy is related to physiological changes that can modify the process of absorption, distribution, metabolism, and excretion and, consequently, the efficacy and toxicity of drugs. However, little is known about furosemide pharmacokinetics and placental transfer in pregnancy. This study evaluated the maternal-fetal pharmacokinetics and distribution to amniotic fluid of furosemide in hypertensive parturient women under cesarean section. Twelve hypertensive parturient women under methyldopa (250 mg/8 h) and/or pindolol (10 mg/12 h) treatment received a 40-mg single oral dose of furosemide 1 to 10 hours before delivery by cesarean section. Blood and urine samples were collected for 12 hours after furosemide administration. At delivery, samples were obtained from maternal and umbilical cord blood (n = 8) to assess the transplacental transfer. Amniotic fluid (n = 4) was collected at the time of delivery. The following furosemide pharmacokinetic parameters were obtained as median (interquartile range): C max , 403 ng/mL (229 to 715 ng/mL

Nonrelevant Pharmacokinetic Drug‐Drug Interaction Between Furosemide and Pindolol Enantiomers in Hypertensive Parturient Women

“…The aim of this work was to evaluate the potential pharmacokinetic drug‐drug interaction of furosemide on (−)‐( S )‐ and (+)‐( R )‐pindolol in a pilot study in hypertensive parturient women. The pharmacokinetics and transplacental transfer of furosemide in hypertensive parturient women were previously reported by our research group 20 …”

“…These findings contribute to safety and efficacy assessment in this orphan population. Considering that significant pharmacokinetic drug‐drug interactions were not observed between pindolol enantiomers and furosemide, 20 these drugs might be safely coadministered during the third trimester of pregnancy in hypertensive women without requirement of dose adjustment. In addition, future studies regarding pharmacodynamic data of this coadministration should be evaluated.…”