Pharmacokinetics, Pharmacodynamics, and Safety of Lisinopril in Pediatric Kidney Transplant Patients: Implications for Starting Dose Selection

Clin Pharmacol Ther. 2015 Jul;98(1):25-33. doi: 10.1002/cpt.127. Epub 2015 May 2.

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-naïve 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-naïve 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.

Trial registration: ClinicalTrials.gov NCT01491919.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Child
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Kidney Transplantation*
  • Lisinopril / administration & dosage
  • Lisinopril / adverse effects
  • Lisinopril / pharmacokinetics
  • Lisinopril / pharmacology*
  • Male

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Lisinopril

Associated data

  • ClinicalTrials.gov/NCT01491919