Nicardipine in pre-eclamptic patients: placental transfer and disposition in breast milk.
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.
Bartels
P A
PA
Department of Hospital Pharmacy, Albert Schweitzer Hospital Dordrecht, Dordrecht, and Erasmus MC Rotterdam, The Netherlands.
Hanff
L M
LM
Mathot
R A A
RA
Steegers
E A P
EA
Vulto
A G
AG
Visser
W
W
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008431:Maternal-Fetal Exchange; D008895:Milk, Human / Q000737:chemistry*; D009529:Nicardipine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D009529:Nicardipine