Nifedipine Levels Research Articles

Effect of repeated Shengmai-San administration on nifedipine pharmacokinetics and the risk/benefit under co-treatment.

Herbal interactions with nifedipine/felodipine through cytochrome P450 (CYP) 3A inhibition is significant in humans. Shengmai-San (SMS), a three-herbal formula of Chinese medicine, is commonly prescribed in Asia populations for cardiovascular disorders. This study aimed to elucidate the impact of SMS on nifedipine/felodipine treatment by the findings from rat pharmacokinetic study of nifedipine to the retrospective cohort study of patients with hypertension. The 3-week SMS treatment increased the systemic exposure to nifedipine by nearly two-fold and decreased nifedipine clearance by 39% in rats. Among the ingredients of SMS component herbs, schisandrin B, schisantherin A, and methylophiopogonanone A, inhibited the nifedipine oxidation (NFO) activities of rat hepatic and intestinal microsomes, as well as human CYP3A4. Methylophiopogonanone A was identified as a time-dependent inhibitor of CYP3A4. After 1:5 propensity score matching, 4,894 patients with nifedipine/felodipine use were analyzed. In patients receiving nifedipine/felodipine, the subgroup with concurrent SMS treatment had a higher incidence of headache (92.70 per 1,000 personyears) than the subgroup without SMS treatment (51.10 per 1,000 person-years). There was a positive association between headache incidence and cumulative doses of SMS (1-60 g SMS: hazard ratio (HR): 1.39; 95% confidence interval (CI): 1.11-1.74; >60 g SMS: HR: 1.97; 95% CI: 1.62-2.39; p < 0.0001). However, patients who had higher cumulative SMS doses had a lower risk of all-cause mortality (1-60 g SMS: HR: 0.67; 95% CI: 0.47-0.94; >60 g SMS: HR: 0.54; 95% CI: 0.37-0.79; p = 0.001). Results demonstrated increased rat plasma nifedipine levels after 3-week SMS treatment and increased headache incidence should be noted in nifedipine/felodipine-treated patients with prolonged SMS administration.

Clinical and pharmacological variables as a risk factor for nifedipine‐induced gingival overgrowth

Gingival enlargement is usually noted within one to two months after the initiation of nifedipine therapy. The aetiology of nifedipine-induced gingival overgrowth is uncertain. The aim of this study was to determine the relationship between plasma and gingival crevice fluid (GCF) nifedipine concentrations and the degree of gingival overgrowth in patients treated with nifedipine, and also to assess the correlations between clinical and pharmacological variables. Eighteen patients taking nifedipine in regular doses for at least six months participated in the study. Gingival enlargement was evaluated with two indices to score vertical and horizontal overgrowth. Gingival index (GI), plaque index (PI), gingival bleeding time index (GBTI), probing depth (PD) and clinical attachment level (CAL) were also evaluated. GCF and plasma nifedipine concentrations were determined by using high performance liquid chromatography. There was no significant difference between responders and non-responders for PI, GI and GBTI. The mean concentration of nifedipine in GCF was significantly greater than concentration in plasma. No significant difference was observed for GCF and plasma nifedipine concentration between responders and non-responders. The present study showed that neither GCF nor plasma nifedipine levels appeared to be a risk factor for nifedipine-induced gingival overgrowth. Improving the oral hygiene in patients using nifedipine may help control the degree of drug-induced gingival enlargement.

Nifedipine serum levels in pregnant women undergoing tocolysis with nifedipine

SummaryThe 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.

The effect of whole‐body sunbed ultraviolet A exposure on the pharmacokinetics of the photolabile drug nifedipine

The calcium antagonist nifedipine absorbs ultraviolet A (UVA) radiation and readily photodegrades in vitro to a toxic nitroso‐pyridine photoproduct. We examined whether whole body exposure of normal subjects to sunbed UVA radiation would affect the pharmacokinetics of nifedipine. Eight healthy, male, Caucasian volunteers (phototypes I–III) participated in this ethically approved, randomised, cross‐over study. Each subject attended on 2 occasions, one week apart, and on each occasion was given a single oral dose (10 mg) of nifedipine following which blood samples were collected at 0, 0.5, 1. 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 7 h. During one of the visits, 15 min after nifedipine ingestion, a whole‐body UVA (sunbed comprising Philips R‐UVA lamps) dose of 70% of the individual's predetermined minimal phototoxic dose was delivered over a period of 17–36 min. Plasma nifedipine levels were measured using a standard reverse‐phase high‐performance liquid chromatography method. The area under the plasma concentration‐time curve (AUC) of nifedipine during the UVA irradiation session (median 206 ng · ml−1 · h−1) was significantly higher than during the non‐irradiation control session (median 174.5 ng · ml−1 · h−1) (P=0.03; 95% C.I. for difference in medians 9.9 to 55.9 ng · ml−1 · h−1). UVA irradiation did not significantly affect any of the other measured pharmacokinetic parameters (Cmax, t1/2, tmax). We demonstrate that sunbed UVA irradiation does not lead to in vivo photodegradation of nifedipine in healthy humans after a single dose. The apparent increase in AUC during UVA irradiation may be due to slightly slower metabolism of nifedipine in the presence of toxic photoproduct(s) or due to blood distribution changes affecting liver blood flow.

Effect of nifedipine on fetal and maternal hemodynamics and blood gases in the pregnant ewe

OBJECTIVE: Our purpose was to determine whether the fetal acidosis and hypoxia previously demonstrated in animal models with maternal nifedipine infusion is the result of a decrease in uteroplacental or fetoplacental blood flow and whether this effect is exacerbated by a higher drug concentration and duration of infusion. STUDY DESIGN: Ten chronically instrumented pregnant ewes (gestational age 0.9 term, term = 145 days) received nifedipine infusions ( n = 7) or vehicle (95% ethanol/water, 3:7) ( n = 3). Three 90-minute periods were evaluated: 5 μg/kg/min infusion (low-dose nifedipine), no infusion, and 10 μg/kg/min (high-dose nifedipine). Paired maternal and fetal blood gases, glucose, lactate, and nifedipine levels were obtained every 30 minutes while hemodynamic parameters were monitored. We determined maternal and fetal blood flows using the radioactive microsphere technique. RESULTS: Although maternal placental blood flows decreased by 25% during low-dose nifedipine ( p < 0.05), this was only transient and there were no other decreases in uteroplacental or fetoplacental blood flow. Fetal blood flow increased to the adrenals and diaphragm with high-dose nifedipine ( p < 0.05). Maternal and fetal lactate levels increased with both doses ( p < 0.05). In addition, fetuses exhibited significant hypoxia (oxygen content fell 0.46 mmol/L) and acidosis (pH fell 0.06 units) throughout the nifedipine infusion and recovery period. Maternal heart rate increased transiently with both doses ( p < 0.05); however, there were no changes in either fetal or maternal mean arterial pressure. Infusion of the vehicle alone did not alter maternal or fetal hemodynamics. Maternal and fetal plasma nifedipine levels reached steady-state by 30 minutes, and maternal/fetal ratios were 0.4 to 0.55. The maternal metabolic clearance rates for low- and high-dose nifedipine were 80.0 and 79.8 ml/min/kg, respectively. Maternal half-life calculation revealed a two-compartment model with a calculated half-life of 2.87 ± 3.15 and 63.57 ± 154.03 (±SD) minutes for the α and β components, respectively. CONCLUSIONS: Maternal nifedipine infusion is associated with hypoxia and acidosis in the sheep fetus, without persistent decreases in uteroplacental or fetoplacental blood flows or blood pressures. These fetal blood gas changes are more severe with high-dose nifedipine and longer duration of infusion and continue to deteriorate even when recovery is allowed. The deterioration of fetal blood gases is out of proportion to the transient decreases in uteroplacental blood flow and demonstrates that another mechanism for this fetal acidosis and hypoxia exists during nifedipine infusion. (Am J Obstet Gynecol 1997;176:922-30.)

Influence of cisapride on the pharmacokinetics and antihypertensive effect of sustained-release nifedipine.

To investigate the clinical significance of interactions between cisapride and sustained-release nifedipine, we compared the plasma nifedipine concentration and blood pressure after administration of nifedipine alone (20 mg) with those obtained after administration of nifedipine cisapride (2.5 mg) in 20 patients with hypertension. The plasma nifedipine level was not altered by cisapride at one hour after administration, but was significantly increased at two (p < 0.01), three (p < 0.01), and four (p < 0.05) hours when compared with the level measured after nifedipine alone. Cisapride significantly decreased the mean blood pressure at three hours (p < 0.05) after administration of nifedipine. The acetaminophen method was used to determine gastric emptying time. The plasma concentration of acetaminophen at 45 minutes after administration was significantly increased by cisapride, suggesting that enhanced gastrointestinal motility might be the basis for the increase in the plasma nifedipine concentration. These results suggest that enhancement of the antihypertensive effect of nifedipine can occur when the drug is prescribed with cisapride, and that caution is needed when using such a combination therapy.

Determination of nifedipine in gingival crevicular fluid: a capillary gas chromatographic method for nifedipine in microlitre volumes of biological fluid

This paper describes a sensitive capillary gas chromatographic (GC) method for the determination of nifedipine in sub-microliter samples of gingival crevicular fluid (GCF) in order to assess if nifedipine is present in the GCF and if so, whether the local tissue concentrations of this drug are an important determinant in the development of gingival overgrowth. Liquid—liquid and solid-phase extraction were combined to give adequate sample clean-up and concentration for measurement by automated capillary GC with electron capture detection. Nifedipine and its principal metabolite, M-I, were analysed in both plasma and GCF in 9 adult male patients who had been taking nifedipine for over six months. M-I could not be measured in GCF. Plasma nifedipine and M-I levels were nomal, but the nifedipine levels found in the GCF of 7 patients (including all those with overgrowth) were remarkably elevated, 15 to 316-fold greater. This massive concentration of nifedipine into the GCF is therefore linked with gingival overgrowth. This is the first time that a GC method has been developed which permits determination of GCF pharmacokinetics of a drug which causes gingival overgrowth, and further investigation will lead to a better understanding of the tissue mechanisms involved.

Single Dose and Steady-State Pharmacokinetic Profiles of Nifedipine GITS Tablets in Healthy Elderly and Young Volunteers

The pharmacokinetics of a once-daily extended-release nifedipine formulation [Gastro-Intestinal Therapeutic System (GITS)] was studied in 23 young males and 24 elderly male and female volunteers, after single and multiple dosing of 60mg nifedipine GITS tablets once daily for 7 days, in an open nonrandomised study. Serial blood samples for plasma nifedipine levels were drawn on days 1 and 7, and the pharmacokinetic profiles of the elderly and young volunteers were compared after both single and multiple dosing.

New developments in sustained-release antihypertensive therapy: Formulation and pharmacokinetic considerations

In order to achieve a consistently absorbed form of nifedipine over 24 hours, a novel formulation approach, INDAS, was used to develop a oncedaily, sustained-release (SR) form of nifedipine that could provide effective control of blood pressure at a low total daily dose. The pharmacokinetic characteristics of this new formulation of nifedipine-SR were compared with those of divided doses of conventional nifedipine. The SR formulation was shown to achieve a lower peak plasma nifedipine level but with a prolonged plasma profile characterized by an extended time to peak plasma levels ( T max, a higher trough plasma level, a longer apparent half-life, and a markedly lower peak-to-trough fluctuation in plasma nifedipine concentrations. In a separate study, the gastrointestinal transit parameters and physical characteristics of the SR tablet were evaluated. This study established that the large intestine is the major site of residence and absorption for this dosage form. The physical erosion and disintegration characteristics of the SR formulation are such that a well-maintained absorption of nifedipine is consistently achieved over the 24 hour dosing interval.

Evaluation of the antianginal effect of nifedipine: influence of formulation dependent pharmacokinetics

Nifedipine capsules t.d.s. and an extended release formulation of nifedipine, nifedipine-ER tablets, given once daily in corresponding daily doses, have been compared with placebo in a double-blind, three-way cross-over study in 24 patients with stable angina pectoris. The objective was to study the influence on the antianginal effect of the different pharmacokinetics of several preparations of nifedipine. All patients received concomitant treatment with beta-adrenoceptor blockers. Antianginal efficacy was assessed by a dynamic exercise test at the end of the dosage intervals, i.e. 8 and 24 h after nifedipine capsules and nifedipine-ER, respectively, as well as 6 h after dosing. Six h after dosing the time of onset of chest pain and total exercise time were longer and total work was significantly higher during both nifedipine-ER (plasma concentration 260 nmol/l) and placebo treatment than after nifedipine capsules (plasma concentration 78 nmol/l). Time to 1 mm ST depression was longer during nifedipine-ER than during nifedipine capsule treatment. No significant difference was seen between nifedipine-ER and placebo. At the end of the dosage interval (24 and 8 h after nifedipine-ER and nifedipine capsules, respectively), no significant difference was found between nifedipine-ER (plasma concentration 75 nmol/l) and the other two treatments. However, placebo was superior to nifedipine capsules (plasma concentration 58 nmol/l) both in the time to onset of chest pain and total exercise time. The lack of effect at the end of the dosage interval was probably due to the subtherapeutic plasma nifedipine level.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Cardiopulmonary Bypass on Plasma Levels of Nifedipine

Blood levels of many medications are acutely lowered by cardiopulmonary bypass (CPB). Because nifedipine is often used to provide protection from coronary ischemia, a determination of the effect of CPB on plasma nifedipine levels might help to determine the potential clinical benefit of nifedipine during and after bypass. Four samples of blood were drawn from each of eight patients undergoing cardiac surgery: one before, two during, and one after CPB. Although plasma levels of nifedipine declined during and after bypass (P less than 0.05, analysis of variance), the time-course and slope of the decline indicate that this was an effect of normal metabolism of the drug rather than an effect of physiologic changes occurring during CPB. An important additional finding was that the majority of patients had subtherapeutic levels of nifedipine before bypass, suggesting that additional nifedipine given during and after surgery might be of benefit. The effect of the CPB circuit itself was also examined in vitro by mixing nifedipine into a pump prime solution that was then recirculated with 2 U of outdated blood while levels of nifedipine were measured for 3 h. Plasma levels did not change in either a CPB circuit exposed to light or kept in a darkened room.

The Effect of Nifedipine on Skin-Flap Survival

Nifedipine, a calcium-channel blocker, is a peripheral vasodilator and has been shown to increase blood flow to skin. The hypothesis that nifedipine would thereby improve skin-flap viability was tested by comparing the extent of necrosis of long pedicle flaps in control and nifedipine-treated rats. Thirty male Sprague-Dawley rats were randomized to receive either 2.5 mg/kg nifedipine in chocolate PO t.i.d. or plain chocolate according to protocols. Serum nifedipine levels were determined by gas chromatography. Dorsal cephalad-based random vascular pedicle flaps (2 X 6 cm) were elevated, sutured to their beds, and photographed for computer-aided surface area determinations. The extent of distal flap necrosis was expressed as a percentage of the total flap area, and differences were studied by one-way analysis of variance. The differences between the mean percentages of necrosis at 1 and 2 weeks for the groups were not statistically significant. We conclude that nifedipine has no effect on the extent of necrosis of the random skin flap in the rat.

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.

Routine measurement of diltiazem and nifedipine levels is unnecessary

Routine measurement of diltiazem and nifedipine levels is unnecessary

The Effect of Sublingual Nifedipine on Coronary Venous Graft Resistance Immediately Following Cardiopulmonary Bypass

The purpose of this study was to determine the effects of sublingual nifedipine administered immediately after discontinuation of cardiopulmonary bypass on coronary graft resistance and systemic hemodynamics. Twenty patients were prospectively randomized into two groups; one given 10 mg sublingual nifedipine after weaning from bypass, the other given a placebo. Coronary graft blood flow was measured under blinded conditions and graft resistance calculated from measurements obtained with an electromagnetic flow probe applied directly to the graft prior to and 15 minutes after drug administration. Serum nifedipine levels were determined immediately before and 15, 30, and 60 minutes after sublingual administration. All patients receiving nifedipine had therapeutic serum levels. Graft resistance in patients given nifedipine decreased a statistically significant average of 27% and increased slightly, but not statistically significantly so, in patients given sublingual placebos. There were no differences between the two groups in cardiac index or pulmonary capillary wedge pressures. We conclude that the administration of sublingual nifedipine to patients in the immediate postbypass period results in therapeutic serum nifedipine levels and decreases coronary graft resistance without affecting cardiac performance.

Total and free steady-state plasma levels and pharmacokinetics of nifedipine in patients with terminal renal failure.

The total and free steady-state plasma levels of nifedipine in patients with renal failure have been compared with those in subjects with normal renal function. Studies were done after administration of nifedipine 10 mg t.d.s. p.o. for 5 days, after i.v. infusion of 4.4 mg, and after a single 10 mg oral dose. The systemic clearance of nifedipine after a single i.v.-dose was higher in subjects with renal insufficiency (854 ml/min) than in those with normal renal function (468 ml/min). After the single oral dose the AUC (6100 ng.min.ml-1) and maximum plasma concentration (75.0 ng.ml-1) were lower than in subjects with normal renal function (19300 ng.ml-1; 122 ng.ml-1). The plasma protein binding of nifedipine averaged 95.5% in normal subjects and 94.8% in patients with renal failure. Although free and total steady-state plasma levels of nifedipine tended to be somewhat lower than normal in renal failure, the changes in pharmacokinetics and decreased protein binding of nifedipine did not result in a significantly different steady-state plasma level of the drug. The blood pressure response to a given plasma nifedipine level appeared to be enhanced in renal failure.

Cardiovascular effects of a nifedipine infusion during fentanyl-nitrous oxide anesthesia in dogs

The hemodynamic effects of a nifedipine infusion were investigated in eight dogs given fentanyl/ pancuronium/nitrous oxide/oxygen anesthesia. Nifedipine (20 μg/kg) was given intravenously over two minutes immediately prior to each 30-minute infusion at 2 μg/kg/min, 4 μg/kg/min, and 6 μg/ kg/min. The range of plasma nifedipine levels obtained was 52.1 to 113.7 ng/mL. The predominant hemodynamic effects were significant reductions systemic vascular resistance (SVR) and mean aortic pressure (MAP), accompanied by a rise in cardiac index and heart rate (HR). Administration of calcium chloride (20 mg/kg) after the nifedipine infusion had no effect on SVR or MAP, but HR was significantly reduced. Serum epinephrine and norepinephrine levels increased after the infusion of nifedipine and suggested that fentanyl did not completely overcome the sympathetic response to the profound vasodilatation. The resulting tachycardia in combination with diastolic hypotension from nifedipine could have a detrimental effect on the myocardial oxygen balance.

Comparative dosing and efficacy of continuous-release nifedipine versus standard nifedipine for angina pectoris: Clinical response, exercise performance, and plasma nifedipine levels

To assess the dosing equivalency and the early and late antianginal efficacy of a gastrointestinal therapeutic system for once-daily, continuous-release nifedipine (N-GITS), 10 patients with stable angina pectoris, who were previously receiving chronic treatment with nifedipine, completed a 12-week trial comparing N-GITS with standard nifedipine. All patients (nine men and one woman; mean age 54 ± 2 [SEM] years) who were receiving standard nifedipine (mean dose 40 ± 5 mg/24 hr) for more than 2 weeks (mean 8 ± 2 months, range 2 to 36 months) were switched to an equivalent once-daily dose (39 ± 5 mg/24 hr) of N-GITS. Standard nifedipine and N-GITS were compared by symptom-limited exercise treadmill tests with a baseline test (A) performed 3 hours after a standard dose of nifedipine. Exercise tests were also performed after 2 weeks of treatment with N-GITS 3 hours (B) and 24 hours (C) after the drug was given, and after 12 weeks of treatment with N-GITS, 24 hours after dosing (D). Results of exercise tests showed no significant difference in mean exercise time—(A) 422 ± 25 vs (B) 426 ± 36 vs (C) 438 ± 35 vs (D) 487 ± 37 seconds. Likewise, there was no significant mean difference in peak double product, resting heart rate, peak exercise heart rate, or resting or maximal systolic blood pressure for any of the exercise test points. Furthermore, five patients (50%) reported side effects with standard nifedipine (all vasodilator-flushing, dizziness, or both), which resolved after treatment with N-GITS ( p ± 0.05). Only one patient (10%) reported side effects with N-GITS (ankle edema). In summary, in patients with angina pectoris, N-GITS at equivalent doses maintains similar exercise performance compared to standard nifedipine without evidence of tolerance and with less nifedipine vasodilator side effects at lower drug levels.

Relation between serum nifedipine concentration and hemodynamic effects in nonobstructive hypertrophie cardiomyopathy

The relation between nifedipine concentration and hemodynamic effects after sublingual administration of 10 or 20 mg was examined in 13 patients with nonobstructive hypertrophie cardiomyopathy (HC). Serum nifedipine concentrations were determined by gas chromatography and were not related to dose. Peripheral vascular resistance decreased as a function of nifedipine concentration (r = −0.63, p < 0.001); this was associated with a concentration-related increase in heart rate (r = 0.56, p < 0.001) and in cardiac index (r = 0.50, p < 0.001). However, evidence for a pure vasodilator effect of nifedipine was inconsistent, in that the change in stroke volume index with nifedipine was not significant. Although stroke volume index increased at nifedipine concentrations between 60 and 120 ng/ml (38 ± 6 to 42 ± 4 ml/m 2, p < 0.01), it decreased at concentrations >120 ng/ml (40 ± 3 to 38 ± 4 ml/m 2, p < 0.01). Moreover, pulmonary artery wedge pressure increased at nifedipine concentrations >120 ng/ml (11 ± 2 to 16 ± 4 mm Hg, p < 0.001), suggesting either depressed left ventricular (LV) systolic function or reduced LV filling. To investigate these possible mechanisms, LV systolic and diastolic function was studied during catheterization with a nonimaging scintillation probe in 6 of the 13 patients. In these subjects, heart rate was held constant by atrial pacing. Nifedipine, at concentrations ≤120 ng/ml did not alter end-diastolic volume, but increased LV stroke volume and ejection fraction; concentrations >120 ng/ml were associated with increased end-diastolic and end-systolic volumes, reduced ejection fraction and end-systolic pressure-volume ratio. No beneficial effects on LV diastolic function were observed at these higher concentrations, as the time constant of isovolumic relaxation increased (32 ± 13 to 60 ± 11 ms, p < 0.01). These results indicate that the hemodynamic effects of nifedipine are related closely to nifedipine concentration in patients with nonobstructive HC. Peripheral vasodilating effects are evident over a wide range of nifedipine levels. At low and medium concentrations, these effects result in augmentation of LV ejection performance; however, negative inotropic effects predominate at high concentrations.

Effects of preoperative calcium entry blocker therapy on alpha-adrenergic responsiveness in patients undergoing coronary revascularization.

Calcium entry blocking drugs (CaEBs) produce vasodilation and, in high doses, modify alpha adrenergic receptor function. Previous laboratory data suggested that CaEBs might alter the response to alpha-adrenergic stimulation. The authors tested the hypothesis that CaEB therapy altered alpha-adrenergic responsiveness in patients chronically treated with CaEBs. Twenty-six consenting patients with coronary artery disease were given a phenylephrine challenge before anesthesia induction and during cardiopulmonary bypass while the aorta was cross-clamped. A log dose response curve was constructed for each patient, and the ED30 (dose producing 30% increase in systemic vascular resistance) was calculated. Nine patients not treated with CaEB served as controls, and 17 patients were treated with nifedipine (n = 7) or diltiazem (n = 10). Mean ED30 was increased approximately three-fold in the CaEB treated groups compared to the control group. However, there was no statistical difference in the ED30 or phenylephrine dose response slopes between CaEB treated and untreated patients. In awake patients, ED30 correlated with nifedipine levels (R = 0.953, P = 0.01). There was a significant (P less than .02) shift in the ED30 from prior to anesthesia to during aortic cross-clamp and cardiopulmonary bypass; ED30 was approximately 50% less and correlated with CaEB level (R = 0.713, P = 0.03). Hemodynamic variables were not different between groups at any interval. Our data suggest that vascular responsiveness to phenylephrine in patients treated with CaEBs is diminished, but similar to that in untreated patients. Vascular responsiveness decreases in awake patients with increasing nifedipine levels.