title: Pharmacokinetics, Pharmacodynamics, and Safety of Lisinopril in Pediatric Kidney Transplant Patients: Implications for Starting Dose Selection.
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.
authors: Department of Pediatrics, New York University, New York, New York, USA.
authors: H
authors: H
authors: Trachtman
authors: Department of Pediatrics, Stanford University, Palo Alto, California, USA.
authors: A
authors: A
authors: Frymoyer
authors: Emmes Corp., Rockville, Maryland, USA.
authors: A
authors: A
authors: Lewandowski
authors: Department of Pediatric Nephrology, Emory University, Atlanta, Georgia, USA.
authors: L A
authors: LA
authors: Greenbaum
authors: Division of Pediatric Nephrology, University of Alabama, Birmingham, Alabama, USA.
authors: D I
authors: DI
authors: Feig
authors: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
authors: D S
authors: DS
authors: Gipson
authors: Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri, USA.
authors: B A
authors: BA
authors: Warady
authors: Division of Nephrology and Hypertension, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
authors: J W
authors: JW
authors: Goebel
authors: Division of Pediatric Nephrology, University of Rochester, Rochester, New York, USA.
authors: G J
authors: GJ
authors: Schwartz
authors: OpAns, LLC, Durham, North Carolina, USA.
authors: K
authors: K
authors: Lewis
authors: Emmes Corp., Rockville, Maryland, USA.
authors: R
authors: R
authors: Anand
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors: U D
authors: UD
authors: Patel
mesh_terms: D000293:Adolescent; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002648:Child; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D016030:Kidney Transplantation; D017706:Lisinopril / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017706:Lisinopril