Nicardipine in pre-eclamptic patients: placental transfer and disposition in breast milk

BJOG. 2007 Feb;114(2):230-3. doi: 10.1111/j.1471-0528.2006.01200.x. Epub 2006 Dec 12.

Abstract

To assess the safety risks to the fetus and neonate caused by maternal use of nicardipine in pre-eclamptic patients, we evaluated the placental transfer and the transfer to breast milk after maternal intravenous administration of nicardipine. In ten pre-eclamptic subjects, nicardipine concentrations of maternal blood (P) and both arterial and venous umbilical cord blood samples (Uarterial and Uvenous) were assessed, and the U/P ratio was calculated as an indication of placental transfer. We found a median transfer of 0.15 (Uarterial/P, range 0.05-0.22) and 0.17 (Uvenous/P, range 0.023-0.22). The highest umbilical cord concentration found after maternal dosage of 4.5 mg/hour was 18 ng/ml, which can be considered as subtherapeutic. Therefore, adverse fetal reactions caused by a direct pharmacological effect of nicardipine are unlikely to occur. Nicardipine levels were determined in 34 breast milk samples of seven women, and were found to be undetectable in 82% of the samples. In six breast milk samples of four different women, nicardipine levels (ranging from 5.1 to 18.5 ng/ml) were detectable during maternal nicardipine dosages ranging from 1 to 6.5 mg/hour. The maximum possible exposure of a neonate to nicardipine was calculated to be less than 300 ng/day, which is an insignificant fraction of therapeutic dosages used in neonates. In conclusion, the exposure of a fetus and neonate to nicardipine through placental transfer and disposition in breast milk expression is low.

MeSH terms

  • Adolescent
  • Adult
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / pharmacokinetics*
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / pharmacokinetics*
  • Female
  • Fetal Blood / chemistry
  • Humans
  • Infant, Newborn
  • Infusions, Intravenous
  • Maternal-Fetal Exchange
  • Milk, Human / chemistry*
  • Nicardipine / administration & dosage
  • Nicardipine / adverse effects
  • Nicardipine / pharmacokinetics*
  • Placenta / metabolism*
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Risk Factors

Substances

  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Nicardipine