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

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

H Trachtman  1 , A Frymoyer  2 , A Lewandowski  3 , L A Greenbaum  4 , D I Feig  5 , D S Gipson  6 , B A Warady  7 , J W Goebel  8 , G J Schwartz  9 , K Lewis  10 , R Anand  3 , U D Patel  11 ; Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee
Collaborators, Affiliations
Clinical Trial

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

H Trachtman et al. Clin Pharmacol Ther. 2015 Jul.

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.

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Conflict of interest statement

CONFLICTS OF INTEREST/DISCLOSURES

Dr. Frymoyer received support from the National Institute of Child Health and Human Development (NICHD; 1K23HD079557 and HSSN275000002). Drs. Anand and Lewandowski receive support from Government Contract HHSN267200700051C (PI: Benjamin). Dr. Patel received support for research from NICHD contract HHSN27500007 and from industry for drug development in adults and children with kidney disease (www.dcri.duke.edu/research/coi.jsp). The remaining authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
CONSORT diagram.
Figure 2
Figure 2
Mean lisinopril concentration versus time after multiple dosing following once-daily dosing in patients who have received a kidney transplant. Patients were stratified by dose group: low dose = 0.1 mg/kg; middle dose = 0.2 mg/kg; and high dose = 0.4 mg/kg. One patient received twice-daily dosing and was not included.
Figure 3
Figure 3
Impact of eGFR on (A) oral clearance allometrically scaled to a 70 kg adult and (B) AUC0–24 dose adjusted to 0.1 mg/kg/day. The geometric mean AUC0–24 dose adjusted to 0.1 mg/kg in historical hypertensive children is shown for comparison.
See this image and copyright information in PMC

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