Serum nifedipine concentrations and response of patients with pulmonary hypertension.

p’ imary pulmonary hypertension is a devastating disease characterized by an elevation in pulmonary artery pressure in the absence of any identifiable underlying causes. Initial experience has shown vasodilator therapy to be relatively ineffective when administered at conventional doses.lm3 However, our group has found that by using high doses of nifedipine, significant reductions in pulmonary vascular resistance and pulmonary artery pressure can be achieved in select patients.4.5 Further, the ability to respond to nifedipine in this manner is associated with a decrease in long-term mortality.6 However, it remains unclear why these patients require such high doses. Therefore, the purpose of this study was to evaluate the pharmacodynamic relationships between serum nifedipine concentration and pulmonary hemodynamic indexes in patients with primary pulmonary hypertension. Eighteen consecutive patients referred to the University of Illinois Hospital Medical Center for evaluation of primary pulmonary hypertension were enrolled in the study. The study protocol was approved by the University of Illinois Institutional Review Board. There were 15 women and 3 men (mean age 35.6 + 8.0 years). Each patient had a thorough evaluation according to the protocol of the National Institutes of Health Primary Pulmonary Hypertension Registry.7 All patients underwent diagnostic right heart catheterization to assess hemodynamic variables. Patients were then transferred to the coronary care unit with a thermodilution flow-directed catheter in the pulmonary artery and an arterial cannula in the femoral artery to monitor systemic pressures. Consecutive 20 mg oral doses of acute-release nifedipine (Procardia; Pfizer, New York, New York) were administered hourly to patients in the coronary care unit until the following : ( 1) maximal decreases in mean pulmonary artery pressure and or pulmonary vascular resistance were achieved; (2) the patient experienced an adverse effect of the drug, requiring discontinuation; or (3) 10 consecutive hourly doses (200 mg) were administered. Systemic and pulmonary pressures were measured 30 and 60 minutes