Pharmacokinetics and placental transfer of magnesium sulfate in pregnant women.

BACKGROUND: Magnesium sulfate is one of the most commonly prescribed intravenous medications in obstetrics. Despite its widespread use, there are limited data about magnesium pharmacokinetics, and magnesium is prescribed empirically without dose adjustment for different indications. OBJECTIVE: The aim of this study was to characterize the pharmacokinetics and placental transfer of magnesium sulfate in pregnant women and to determine key covariates that impact the pharmacokinetics. STUDY DESIGN: This is a prospective pharmacokinetic cohort study of pregnant women who were prescribed magnesium sulfate for preeclampsia, preterm labor, or extreme prematurity. Women received a 4-g loading dose and 2 g/h maintenance dose as clinically indicated. Maternal blood samples were obtained before and at multiple time points during and after magnesium administration. Cord blood also was sampled at delivery. A population pharmacokinetic approach that used a nonlinear mixed-effects modeling was used to characterize magnesium disposition. RESULTS: Pharmacokinetic profiles of 111 pregnant women were analyzed. Magnesium clearance was 3.98 L/h in preeclamptic women and 5.88 L/h non-preeclamptic women. Steady-state concentration of magnesium was 7.2 mg/dL in preeclamptic women compared with 5.1 mg/dL in non-preeclamptic women. Maternal weight significantly impacted time to steady state. The ratio of the mean umbilical vein magnesium level to the mean maternal serum magnesium level at the time of delivery was 0.94 ± 0.15. CONCLUSIONS: The study accurately characterizes the pharmacokinetics of magnesium administered to pregnant women. Preeclamptic status and maternal weight significantly impact serum magnesium levels. This pharmacokinetic model could be applied to larger cohorts to help tailor magnesium treatment and account for these covariates.

Pharmacokinetics of nifedipine slow-release during sustained tocolysis.

OBJECTIVE: The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system (GITS) tablets. The aim of this study was to determine nifedipine slow-release half-life and distribution volume in pregnant women and to compare these with pharmacokinetic parameters of nifedipine in non-pregnant subjects described in the literature. MATERIALS: This is a study parallel to a trial studying women with threatened preterm labor between 26 + 0 and 32 + 2 weeks after initial tocolysis and a completed course of corticosteroids, who were randomly allocated to maintenance nifedipine (slow-release tablets 20 mg 4 times daily) or placebo. Exclusion criteria for the pharmacokinetic study were contra-indications for nifedipine, impaired liver function, and concomitant intake of inhibitors or inducers of the cytochrome P450 3A4 isoenzyme. Blood samples for measuring nifedipine plasma concentrations were drawn at t = 0, t = 12 hours, t = 24 hours, t = 48 hours, t = 72 hours, t = 7 days, and t = 9 days. METHODS: Pharmacokinetic parameters were estimated using iterative two-stage Bayesian population pharmacokinetic analysis by MWPharm© software. The study was designed to establish a correlation between body weight and nifedipine plasma level. RESULTS: The pharmacokinetic parameters of nifedipine slow-release tablets were determined from the data of 8 pregnant women. Nifedipine slow-release had a half-life of 2 - 5 hours, a mean distribution volume of 6.2 ± 1.9 L/kg (calculated while using a fixed biological availability of 0.45 taken from the literature due to lack of intravenous data in this population) compared to a half-life of 6 - 11 hours, and a distribution volume of 1.2 - 1.3 L/kg described in non-pregnant subjects in the literature. None of the women delivered during study medication. Study medication was continued for the duration of the pharmacokinetic study (9 days) in all women. A correlation between nifedipine plasma levels and maternal body weight was not demonstrated. This may have been caused by lack of power. CONCLUSION: Pregnant subjects in this study, using nifedipine slow-release tablets, showed a larger volume of distribution and a shorter elimination half-life than for non-pregnant subjects as published in the literature.

Preparation and evaluation of ritodrine buccal tablets for rational therapeutic use.

Ritodrine hydrochloride (RD-HCl) tablets containing alginate (AL) and lactose (LC) with or without microcrystalline cellulose (MC) as excipients were produced as a buccal dosage form. The RD-HCl (2 mg) tablets with AL/LC but no MC swelled and dissolved gradually in the in vitro dissolution test. The tablet showing the fastest dissolution and highest drug release rate, called Tablet A1, was selected as a tablet to show rapid and prolonged absorption. However, in the in vivo buccal absorption test using rats, it could not give a plasma concentration over the human minimal effective level (15 ng/mL). The modified tablet containing AL, LC, MC and RD-HCl (4 mg), named Tablet B/MC, showed better hardness and faster drug release. Tablet B/MC gave a plasma concentration over the human effective level within 15 min, and the plasma concentration was maintained at >15 ng/mL over 4 h. Moreover, the deconvolution analyses demonstrated that a prolonged high absorption rate could be achieved in vivo best with Tablet B/MC. Tablet B/MC improved the pharmacokinetic profile in comparison with Tablet A1 and the solution dosage form. The RD-HCl buccal tablets with AL, LC and MC as excipients are suggested to be possibly useful for the treatment of premature labor.

Maternal magnesium sulphate exposure predicts neonatal magnesium blood concentrations.

Tocolytic use of magnesium sulphate is associated with excess neonatal mortality and has been proposed to follow a dose-response relationship. This study aimed to define the correlation between maternal and neonatal magnesium blood concentrations. Magnesium blood concentrations were retrospectively obtained for mother-neonate pairs who were cared for at an Intermountain Healthcare facility from January 2009 to October 2011. Complete data were available for 231 mother-neonate pairs. Mean (±SD) maternal and neonatal magnesium concentrations were 5.43±1.69 and 2.98±0.94 mg/dL, respectively. Maternal and neonatal magnesium concentrations were highly correlated (p<0.001). In univariate analyses, residual unexplained variability was high (r2=0.19). However, further multivariate analyses revealed that caesarian section, severe pre-eclampsia and Apgar score at 5 min. were significantly associated with neonatal magnesium concentrations (p<0.05 for all). Maternal magnesium concentrations correlate with neonatal exposure. This finding suggests that maternal monitoring deserves further evaluation as a marker of foetal toxicity.

In vivo absorption study of ritodrine hydrochloride in the buccal administration to rats.

BACKGROUND: Although ritodrine (RD)-hydrochloride (HCl), named RD-HCl, is widely used in the treatment of premature labor by intravenous prolonged infusion or frequent oral dosing of tablets, those administrations often lower patients' quality of life (QOL) or cause undesirable side effects, such as tachycardia; therefore, in this study, the potential usefulness of buccal administration as a novel administration method was examined in vivo. METHOD: First, the HPLC method was assessed for the determination of plasma RD concentration. Then, after RD-HCl solution in saline was administered intravenously (1 mg/kg), intragastrically (10 mg/kg) or buccally (10 mg/kg) in rats, the plasma concentration-time profiles were investigated, and the absorption extent and rate compared. RESULTS: The present modified determination method by HPLC with fluorescence detection (Ex. 278 nm, Em. 306 nm) was suitable to analyze the plasma level at 8-200 ng/mL. Buccal administration gave the best plasma concentration-time profile for maintenance of an effective plasma level and fewer side effects. Absorption rates calculated by deconvolution also supported better sustained absorption in buccal dosing. CONCLUSION: Buccal application of RD-HCl was demonstrated to be a potentially useful dosing method in the treatment of premature labor with RD-HCl.

Pharmacokinetics of ritodrine diastereomers in patients pregnant with singletons and twins.

OBJECTIVE: The chiral pharmacokinetics and pharmacodynamics of ritodrine in patients pregnant with singletons and twins were investigated to determine the optimal use of ritodrine. METHODS: Eight and 20 patients with threatened preterm delivery of singletons and twins, respectively, were infused with ritodrine diastereomers. Serum concentrations of the drug were then measured using a newly developed method of chiral high-performance liquid chromatography. RESULTS: Almost double the dosage of racemic ritodrine was required to prolong pregnancies with twins compared with those of singletons (2.20 +/- 1.06 vs. 1.24 +/- 0.36 microg/min per kilogram; p < 0.0001). The mean ratios of (-)-ritodrine to (+)-ritodrine in singleton and twin pregnancies were 1.17 +/- 0.10 and 1.16 +/- 0.10, respectively. However, the serum concentration and dosage ratio (C/D ratio) of (-)-ritodrine as significantly higher than that of (+)-ritodrine (p < 0.0001), whereas the clearance of (-)-ritodrine was significantly lower than that of (+)-ritodrine (p < 0.0001). A comparison of the gestation period (weeks) and diastereomer clearance did not reveal significant regression in the total analysis of the data obtained from singleton and twin pregnancies. CONCLUSION: These results indicate that the clinical effectiveness of ritodrine diastereomers should be evaluated and that administration guidelines should be established based upon serum concentrations so that ritodrine can be more effectively administered to pregnant patients carrying either singletons or twins.

Nifedipine concentration in maternal and umbilical cord blood after nifedipine gastrointestinal therapeutic system for tocolysis.

OBJECTIVE: To determine nifedipine concentrations in maternal plasma at steady state, and maternal and umbilical cord plasma at delivery, after tocolysis with nifedipine gastrointestinal therapeutic system (GITS) tablets. DESIGN: Prospective clinical pharmacokinetic study. SETTING: Department of Obstetrics at the Zurich University Hospital. POPULATION: Pregnant women treated for threatened preterm labour. METHODS: GITS dosage titrated to clinical response (30-150 mg/day). Nifedipine concentrations by high-performance liquid chromatography and turbo ion spray tandem mass spectrometry. MAIN OUTCOME MEASURES: Steady-state nifedipine concentrations in maternal blood and nifedipine concentrations in maternal and corresponding umbilical cord blood at delivery. RESULTS: Steady-state nifedipine concentrations (micrograms/l, mean +/- SE) were 54 +/- 6 (all doses, n = 31), 38 +/- 8 (60 mg/day, n = 13), and 92 +/- 12 (150 mg/day, n = 7) (P < 0.002). Umbilical cord and maternal concentrations both declined in a ln-linear regression with elimination half-lives of 20.4 and 17.4 hours. Linear regression showed a correlation between umbilical and maternal concentrations of 0.77 +/- 0.1 (n = 21, mean +/- SE). CONCLUSIONS: Steady-state plasma nifedipine concentrations after repeated dosing with nifedipine GITS 30-150 mg/day in pregnant women with preterm labour do not exceed 100 micrograms/l; fetal levels are 77% of maternal levels.

Nifedipine pharmacokinetics and plasma levels in the management of preterm labor.

The aim of this study was to determine if the dose regimen of nifedipine used for tocolysis was effective to achieve uterine quietness, and at which plasma concentration levels this tocolysis was achieved to optimize our dose regimen of nifedipine. In women with preterm labor, nifedipine was administered orally to achieve uterine quietness to prevent preterm birth. Patients (n = 5) were administered 10 mg nifedipine capsules (Adalat capsules, Bayer AG) orally every 15 minutes up to 40 mg in the first hour, and were subsequently given 1 tablet of 20 mg nifedipine slow release (Adalat retard, Bayer AG) t = 90 min. Plasma levels of nifedipine were measured at regular intervals during the first 4 hours after starting tocolysis. In all 5 patients tocolysis was achieved with nifedipine. Peak plasma concentration of nifedipine was 127.2 +/- 44 ng/mL at 1.2 +/- 0.1 hours. Mean plasma concentrations of nifedipine was 67.4 +/- 28.4 ng/mL. In all patients, tocolysis was achieved during the 4 hours of blood sampling. There were no adverse hemodynamic side effects seen before and after starting tocolysis with nifedipine. Initial dose regimen of 4 times 10 mg nifedipine capsule orally in the first hour, followed by 20 mg slow release nifedipine at t = 90 min is effective in achieving tocolysis in women with preterm labor. In steady state, the mean nifedipine plasma concentration to achieve tocolysis is about the half of that measured after initial tocolysis. Use of nifedipine for preterm labor was not associated with any adverse hemodynamic side effects.

Nifedipine serum levels in pregnant women undergoing tocolysis with nifedipine.

The objective of our cross-sectional, observational study was to investigate nifedipine serum levels in pregnant women undergoing tocolysis. A total of 24 pregnant women, 22-34 weeks' gestation, who were administered nifedipine for treatment of pre-term labour, were enrolled in the study. Blood samples were taken 12 h after the oral application of 60 mg nifedipine in 'continuous release' form (Adalat CR 60). Nifedipine serum levels were measured with liquid chromatography. Nifedipine serum levels spread between 6 and 101 ng/ml (17-292 nmol/l). There was no correlation between nifedipine levels and body mass index (BMI), or between nifedipine levels and gestational age. During nifedipine tocolysis, 11 of 24 patients (45.8%) had mild side-effects, mostly headache. The side-effects were not dose-related. Despite the standardised dosage and standardised blood sampling nifedipine serum levels spread in a wide range. There is no need to adjust the dose of nifedipine to BMI or to gestational age.

Adverse maternal and neonatal outcome of prolonged course of magnesium sulfate tocolysis.

BACKGROUND: Magnesium sulfate continues to be widely used as a tocolytic agent despite a paucity of evidence supporting its use. Many practitioners use prolonged courses of magnesium sulfate, sometimes for months. This study was conducted to determine maternal and neonatal outcome of patients exposed to prolonged tocolytic magnesium sulfate. METHODS: A retrospective review of maternal and neonatal charts (1995-2003) of pregnancies that received tocolytic magnesium sulfate. Cases who received magnesium sulfate >48 h (n=78) were compared to controls who received it < or =48 h (n=77) for maternal side effects and neonatal outcome. RESULTS: Cases were more likely to be nulliparous (55.1% versus 37.7%, p=0.044), multiple gestations (33.3% versus 10.4%, p=0.001), and of lower gestational age (29.0+/-3.9 versus 30.5+/-3.8 weeks, p=0.017) compared to controls. The median magnesium sulfate infused was 154 (78-5,500) versus 54 (8-86) g (p<0.001) and the highest maternal magnesium level was 6.5+/-1.7 versus 5.6+/-1.9 mg/dl (p=0.002) in cases and controls, respectively. Cases were more likely to have > or =1 adverse side effect (30.8% versus 15.6%, p=0.045). The median neonatal magnesium level was significantly higher in cases (3.3 (1.4-7.2) versus 2.6 (1.1-5.2) mg/dl, p=0.016); however, neonatal mortality and other neonatal morbidity rates were similar in both groups. Abnormal bone mineralization was encountered in 3 neonates (cases). CONCLUSIONS: Maternal morbidity rate is higher with prolonged intake of tocolytic magnesium sulfate compared to < or =48-h regimen. Despite similar neonatal morbidity and mortality rates, bone demineralization in the neonates may be encountered.

Brain lesions in newborns exposed to high-dose magnesium sulfate during preterm labor.

High-dosage, tocolytic magnesium sulfate (MgSO4) administered to pregnant women during preterm labor can be toxic, and sometimes lethal, for their newborns (Cochrane Database of Systematic Reviews (relative mortality risk 2.82, 95% confidence interval 1.2-6.6)). Based on the results of the Magnesium and Neurologic Endpoints Trial and the work of many others, a unifying triangular concept is proposed to account for the increased prevalence of brain lesions, with their likely resultant mortality, in neonates and infants exposed to high-dose MgSO4 in the context of preterm labor. We review the evidence that: (1) elevated circulating levels of serum ionized magnesium occurring in mothers, and therefore in their babies, at the time of delivery are associated with subsequent neonatal intraventricular hemorrhage (IVH); (2) neonatal IVH is strongly associated with lenticulostriate vasculopathy (LSV), an unusual mineralizing lesion involving the thalami and basal ganglia of the neonate; and, (3) exposure to 50 g or more of tocolytic MgSO4 during preterm labor is associated with the development of LSV.

Steady-state maternal and fetal plasma concentrations of glyceryl trinitrate (GTN) in the preterm sheep.

The administration of glyceryl trinitrate (GTN; nitroglycerin) is increasing during preterm pregnancies, yet its disposition and, importantly, the extent of fetal exposure remain to be elucidated. When used as a tocolytic (pharmacological agent that stops uterine contractions), it is administered transdermally (24-48 h). Here, we quantified the maternal and fetal steady-state plasma concentrations of maternal intravenous GTN in preterm sheep and continuously monitored maternal and fetal vascular parameters to observe possible dose-dependent vascular effects. Preterm (120 days gestation) pregnant sheep (n = 6) were instrumented with maternal femoral arterial (MA) and venous (MV) and fetal femoral arterial (FA) and umbilical venous (UV) polyethylene blood-sampling catheters. During maternal GTN infusion (3.0 micro g.kg-1.min-1, 60-min duration) the steady-state GTN concentrations ([GTN]) were as follows: MA, 98.6 +/- 9.0 nM; UV, 17.4 +/- 7.6 nM; and FA, <5 nM. There were no changes in maternal and fetal mean arterial pressure and heart rate or in uterine activity. Overall, the steady-state [GTN] was established by 5 min, and the UV/MA ratio of [GTN] was 0.18. The FA [GTN] (<5 nM) indicates that the fetus cleared essentially all GTN in the UV, and the maternal and fetal heart rate and mean arterial pressure appear to be independent of maternal GTN infusion.

Effects of meluadrine tartrate on maternal metabolic responses and fetal hemodynamics in pregnant goats.

This study was designed to elucidate the effects of meluadrine tartrate on maternal metabolic responses and fetal hemodynamics in unanesthetized, chronically instrumented pregnant goats. After the administration of meluadrine tartrate to pregnant goats or directly to fetuses, changes in heart rate (HR), arterial blood pressure and arterial blood pH, gasses, electrolytes and metabolic responses were measured. The constant administration of meluadrine tartrate (0.1 microg. kg(-)(1). min(-)(1)) to pregnant goats resulted in the increases of maternal HR, glucose and free fatty acid and the decrease of maternal blood K(+) concentration. The direct escalating administration of meluadrine tartrate (0.01, 0.03 and 0.1 microg. kg(-)(1). min(-)(1)) did not increase the fetal HR, while ritodrine hydrochloride (0.3, 1 and 3 microg. kg(-)(1). min(-)(1)) to fetuses increased the fetal HR dose-dependently. The present study suggests that meluadrine tartrate has a mild influence relative to the effects of ritodrine to the maternal metabolic responses and fetal cardiovascular function.

Comparison of oxytocin and oxytocin antagonist metabolism in the plasma of pregnant humans and baboons.

Oxytocin antagonists may be useful in inhibiting the uterine contractions of preterm labor. One such compound is TT-235 (previously referred to as Antag III). The purpose of this study was to compare the resistance of TT-235 and oxytocin to enzymatic degradation by oxytocinase in the blood of humans and baboons during their 3rd trimester of pregnancy. Blood samples from pregnant women and baboons not in labor were incubated in vitro with known amounts of oxytocin and TT-235. Samples were collected at 0, 15, 30, 45, and 60 min for oxytocin analysis and at 0, 10, 60, and 360 min for TT-235 analysis. Oxytocin was analyzed by radioimmunoassay after extraction, while TT-235 was analyzed by radioreceptor assay. In human blood, oxytocin was readily metabolized with >83% disappearance over the 60-min incubation period. In contrast, TT-235 was stable up to 360 min of incubation. In the baboon, oxytocin did not diminish over the 60-min incubation period. The level of TT-235 was similar to that in human blood without change over 360 min of incubation. This study suggests (1) that in contrast to blood from pregnant humans, blood from pregnant baboons lacks oxytocinase at least in vitro and (2) that TT-235 is resistant to enzymatic degradation by human blood, implying that this oxytocin antagonist may have a prolonged activity in vivo in humans.

Association between maternal serum ionized magnesium levels at delivery and neonatal intraventricular hemorrhage.

OBJECTIVES: To determine whether magnesium sulfate (MgSO(4)) exposure is associated with a reduced risk for neonatal intraventricular hemorrhage (IVH). STUDY DESIGN: In a randomized, controlled trial, women in preterm labor were randomly assigned to receive MgSO(4), "other" tocolytic, or saline control. At delivery, we collected maternal antecubital and umbilical cord blood for determination of serum ionized magnesium levels. Neonatal IVH was diagnosed by cranial ultrasonogram. RESULTS: Among 144 infants, 24 were diagnosed with IVH. Using crude intention-to-treat analysis, we found that 18% (13/74) of survivors exposed after birth to MgSO(4) had IVH compared with 16% (11/70) of babies who were not exposed. Infants who had IVH were more likely to have been delivered by mothers with higher serum ionized magnesium (Mg) levels (0.75 vs 0.56 mmol/L) (P =.01). Using multivariable logistic regression, we confirmed that higher Mg levels are a significant predictor of neonatal IVH (adjusted odds ratio, 15.8; 95% CI, 1.4-175.0) even when adjusted for birth weight, gestational age, antenatal hemorrhage, and neonatal glucocorticoid exposure. CONCLUSIONS: In mothers with preterm labor, our data indicate that antenatal MgSO(4) exposure may be associated with an increased risk for IVH among their newborns.

[Autotransfusion during caesarean section with blood containing p salbutamol without adverse effects]. / Autotransfusion en cours de césarienne de sang contenant du salbutamol sans effets indésirables.

We report the case of a patient presenting with a placenta praevia and who donated autologous blood while she had beta 2-agonist tocolysis. As the restitution of blood containing salbutamol at therapeutic concentration may induce uterine atony and cardiovascular symptoms, we monitored maternal clinical signs and plasma concentrations of salbutamol when autologous blood was retransfused after the end of Caesarean section. The maternal plasma beta 2-agonist levels during tocolysis were in agreement with the usual therapeutic concentrations. The beta 2-agonist infusion was discontinued 30 minutes before the subarachnoid blockade and the blood concentration measured at the time of skin incision was below the therapeutic threshold. The retransfusion of autologous blood neither raised the salbutamol concentration above the therapeutic threshold value, nor induced any clinical symptoms. After Caesarean section the retransfusion of autologous blood containing therapeutic concentration of salbutamol seems to be innocuous.

Placental passage of the oxytocin antagonist atosiban.

OBJECTIVE: We wanted to determine the degree of placental transfer of atosiban (Antocin), an oxytocin antagonist, in pregnant women at term. We also assessed the effects of the infusion on umbilical cord blood gases at birth and the maternal hematocrit drop after cesarean section. STUDY DESIGN: Eight women undergoing elective cesarean section at term were studied. Each received an infusion of 300 micrograms/min of atosiban over 208 to 443 minutes; the infusion was continued up to the time of cord clamping. Uterine vein and umbilical blood samples were obtained simultaneously. They were assayed by specific radioimmunoassay. Cord blood gases were obtained and compared with those from a control group of women undergoing elective cesarean section. RESULTS: The mean (+/- SD) maternal uterine vein concentration was 331.9 +/- 42.9 ng/ml, compared with 42 +/- 13 ng/ml in the umbilical vein (p < 0.05). The mean maternal/fetal was 12 +/- 0.03, which was not affected by the length of infusion. There was no significant difference in the hematocrit drop between the cesarean delivery groups: 5.9 +/- 0.4 for the control group versus 5.8 +/- 1.1 for the atosiban group (p > 0.1). The mean cord pH was 7.27 for the atosiban group versus 7.27 for the control group (n = 141) (p > 0.1). One year follow-up of the infants (n = 7) was normal. CONCLUSIONS: Our results show minimal placental transfer of atosiban. Drug levels did not increase with longer infusions, and no effect was seen on umbilical cord gases. Administration of atosiban even at high doses up to the time of delivery did not increase maternal blood loss at cesarean section.

Magnesium tocolysis: serum levels versus success.

The relationship between maternal serum magnesium levels and tocolytic success is poorly established. We performed a retrospective analysis of 101 episodes of preterm labor treated with magnesium sulfate and compared the initial, average, and maximum serum magnesium levels with tocolytic success at 48 hours and 7 days. There was no difference in the proportions of tocolytic success when serum levels were less than 6 mg/dl compared with levels of greater than or equal to 6 mg/dl. Similar analyses on either side of 5 mg/dl also revealed no significant relationship. Mean serum magnesium levels in patients with successful tocolysis were statistically similar to those of patients in whom tocolysis failed. Multiple logistic regression analysis also failed to establish a positive relationship between serum magnesium levels and tocolytic success. We conclude that serum magnesium levels alone should not serve as an end point of therapy.

Nifedipine pharmacokinetics during preterm labor tocolysis.

Nifedipine, a calcium entry blocker, has known relaxing effects on the myometrium. Thirteen women in preterm labor received nifedipine for tocolysis. Blood samples obtained serially during treatment and at the time of delivery were assayed for maternal and neonatal nifedipine concentrations. The peak concentration of nifedipine during sublingual therapy ranged from 23.4 to 197.9 ng/ml and reflected substantial interpatient variability. The mean (+/- SD) measurable trough value in patients who received 20 mg of nifedipine orally every 6 hours was 7.2 +/- 5.5 ng/ml. The maternal mean half-life of nifedipine was 81 minutes (range 49 to 137 minutes). At delivery, neonatal nifedipine levels were nondetectable in 6 of the 11 neonates available for study; in 5, values ranged from 29.5 to 1.8 ng/ml. From these results we conclude that both sublingual and oral nifedipine treatment results in variable but usually measurable maternal plasma concentrations and that placental transfer of nifedipine occurs.