Pharmacokinetics and Pharmacodynamics of Nifedipine in Children with Bronchopulmonary Dysplasia and Pulmonary Hypertension

Abstract

ABSTRACT. 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 tLmol/kg (0.5 rug/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 t,;, were 0.456 ± 0.194 h-I and 1.8 ± 0.8 h, respectively. Nifedipine caused a significant (p ::s 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 J-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. Based on these results, an initial oral maintenance regimen of 1.44 tLmol/kg (0.5 mg/kg) every 6 h would be needed for this patient population. If the safety and efficacy after chronic therapy can also be shown, nifedipine may prove to be an important therapeutic addition to the management of children with bronchopulmonary dysplasia and pulmonary hypertension.

Pediatric Pulmonary Hypertension

“…279,281,282 Nifedipine can acutely lower PAP and PVR in children with BPD, but the effects of nifedipine on PAP were not different from the effects of supplemental oxygen alone. Compared with a short-term study of iNO reactivity in BPD, the acute response to CCB was poor, and some infants developed systemic hypotension.…”

Pulmonary Artery Hypertension in Formerly Premature Infants With Bronchopulmonary Dysplasia: Clinical Features and Outcomes in the Surfactant Era

“…Other investigators demonstrated improvement in PVR in patients with BPD and PAH in response to prostacyclin 12,20 and variable responsiveness to calcium channel blockers. 6,30 Evaluation of PAH in Infants With BPD The prevalence of and risk factors for PAH in infants with BPD are not known, which complicates the development of an effective screening strategy. In the present study, almost one half of the 18 patients with systemic or suprasystemic RV pressure were SGA, which suggests that SGA infants may be at increased risk for severe PAH.…”

Upregulation of vascular calcium channels in neonatal piglets with hypoxia-induced pulmonary hypertension

“…In this regard, calcium channel blockers (CCBs) have been used as long-term vasodilator therapies for PAH in the pediatric population that responds positively to an acute vasodilator test (4,30,32). The CCBs exert their vasodilator effect by binding with high affinity to long-lasting or "L-type" calcium (Ca L ) channels in vascular smooth muscle cells (VSMCs) to attenuate voltage-gated Ca 2ϩ influx.…”