Pharmacokinetics and pharmacodynamics of nifedipine in children with bronchopulmonary dysplasia and pulmonary hypertension.
The pharmacokinetics and associated pharmacodynamics of nifedipine were studied in nine children aged 5 to 68 mo with bronchopulmonary dysplasia and pulmonary artery hypertension after a single oral dose of 1.44 mumol/kg (0.5 mg/kg). In the cardiac catheterization laboratory, hemodynamic measurements were made in duplicate just before the nifedipine dose and at 5 min and 0.5 and 1.0 h after the dose. The plasma nifedipine concentration was measured by HPLC at each of the above times and at 2.5, 4.0, 6.0, and 8.0 h after the dose. The mean (+/- SD) maximum plasma concentration and the time to maximum plasma concentration were 243.4 +/- 194.5 nmol/L and 1.0 +/- 0.8 h, respectively. The mean area under the plasma concentration-time curve was 761 +/- 509 nmol.h/L. The mean elimination rate constant and t1/2 were 0.456 +/- 0.194 h-1 and 1.8 +/- 0.8 h, respectively. Nifedipine caused a significant (p less than or equal to 0.05) reduction in the mean pulmonary artery pressure by 5 min and in the mean pulmonary vascular resistance index and mean aortic pressure by 30 min, and these reductions remained significant through the 1-h measurement interval. The magnitude of acute hemodynamic response correlated closely with the plasma nifedipine concentrations. No significant change occurred in the mean arterial oxygen saturation or cardiac index during the study period. The percentage changes from baseline in the mean pulmonary artery pressure and mean pulmonary vascular resistance index were approximately double the percentage change in the mean aortic pressure, suggesting that nifedipine had some degree of selective impact on the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnson
C E
CE
College of Pharmacy, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor 48109.
Beekman
R H
RH
Kostyshak
D A
DA
Nguyen
T
T
Oh
D M
DM
Amidon
G L
GL
D000284:Administration, Oral; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002675:Child, Preschool; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009543:Nifedipine / Q000493:pharmacokinetics / Q000494:pharmacology*
D004232:Diuretics; D009543:Nifedipine