No abstract

No abstract

C ompared to other tocolytic agents, the use of nifedipine has been associated with longer postponement of delivery, fewer maternal adverse effects, fewer neonatal intensive care unit admissions, along with oral dosing and lower drug and administration costs. Nifedipine is not licensed for tocolysis in Switzerland, but it was studied in a formulation providing superior slow-release characteristics, that is, nifedipine gastrointestinal therapeutic system (GITS) tablets. This prospective clinical pharmacokinetic study determined maternal plasma concentrations at steady state and maternal and umbilical cord plasma concentrations at delivery as an estimate of transplacental drug transfer.Patients had a singleton pregnancy, gestational age >19.0 but r35.0 weeks, threatened preterm labor, and tocolysis with nifedipine GITS for Z5 days. The 20, 30, or 60 mg doses of nifedipine GITS tablets were titrated to clinical response with a maximum dose of 150 mg/d. Nifedipine was assayed by high-performance liquid chromatography. The primary end point of the study was the steady-state maternal plasma concentration. Secondary end points were maternal and umbilical cord plasma concentrations at delivery and the dose-response relationship.Forty women completed the study; 90% had threatened preterm labor as the only complication. Eight infants had respiratory distress syndrome and 14 required admissions to the neonatal intensive care unit. In 31 women before delivery, nifedipine doses at steady state were 30 to 150 mg/d; plasma drug concentrations were 6.5 to 148.0 mg/L. Drug concentrations, based on linear regression analysis, were dose dependent, with significant differences between 60 and 150 mg and 90 and 150 mg dosages. Thirteen women delivered in <24 hours, 4 women at 24 to 72 hours, and 4 women at >72 but r144 hours after the last dose. Maternal and umbilical cord plasma concentrations decreased with time to <1 mg/L 80 hours after the last dose. The mean estimated half-lives in maternal plasma and umbilical cord plasma were 17.4 hours and 20.4 hours, respectively. Multiple regression of nifedipine concentrations, time interval, and dose showed no correlation with dose. Mean umbilical cord drug plasma concentration at delivery was 12.4 mg/L compared with mean maternal plasma concentration of 19.8 mg/L, for a ratio of 0.77% and 77% placental drug transfer. Maternal adverse events were mild or moderate and transient in nature and none were related to higher drug plasma concentrations. No correlation was found between higher umbilical cord blood concentrations and poor/adverse fetal outcomes.Although the study was not designed to assess the efficacy of nifedipine, the steady-state plasma concentrations did not exceed 100 mg/L, falling within the established therapeutic range of 10 to 100 mg/L.

No abstract

No abstract