Pharmacokinetics, Pharmacodynamics, and Safety of Lisinopril in Pediatric Kidney Transplant Patients: Implications for Starting Dose Selection
03/2015
Journal Article
Authors:
Trachtman, H.;
Frymoyer, A.;
Lewandowski, A.;
Greenbaum, L. A.;
Feig, D. I.;
Gipson, D. S.;
Warady, B. A.;
Goebel, J. W.;
Schwartz, G. J.;
Lewis, K.;
Anand, R.;
Patel, U. D.
Volume:
98
Pagination:
25-33
Issue:
1
Journal:
Clin Pharmacol Ther
PMID:
25807932
URL:
https://www.ncbi.nlm.nih.gov/pubmed/25807932
DOI:
10.1002/cpt.127
Keywords:
Adolescent Angiotensin-Converting Enzyme Inhibitors/administration & dosage/adverse effects/pharmacokinetics/*pharmacology Child Female Humans Hypertension/*drug therapy *Kidney Transplantation
Lisinopril/administration & dosage/adverse effects/pharmacokinetics/*pharmacology Male
Abstract:
Hypertension in pediatric kidney transplant recipients contributes to long-term graft loss, yet treatment options--including angiotensin-converting enzyme inhibitors--are poorly characterized in this vulnerable population. We conducted a multicenter, open-label pharmacokinetic (PK) study of daily oral lisinopril in 22 children (ages 7-17 years) with stable kidney transplant function. Standard noncompartmental PK analyses were performed at steady state. Effects on blood pressure were examined in lisinopril-naive patients (n = 13). Oral clearance declined in proportion to underlying kidney function; however, in patients with low estimated glomerular filtration rate (30-59 ml/min per 1.73m(2)), exposure (standardized to 0.1 mg/kg/day dose) was within the range reported previously in children without a kidney transplant. In lisinopril-naive patients, 85% and 77% had a >/= 6 mmHg reduction in systolic and diastolic blood pressure, respectively. Lisinopril was well tolerated. Our study provides initial insight on lisinopril use in children with a kidney transplant, including starting dose considerations.
