Pharmacokinetic drug-drug interaction of calcium channel blockers with cyclosporine in hematopoietic stem cell transplant children.

Abstract

BACKGROUND:

Cyclosporine (CsA) is frequently responsible for hypertension in bone marrow transplant children. Calcium channel blockers (CCBs) are considered to be the best treatment for CsA-induced hypertension, but they may alter the exposure and the effect of CsA by inhibiting the CYP3A4 pathway of CsA metabolism or P-gp. However, the inhibitory effect on CYP3A4 may vary among CCBs.

METHODS:

This study aimed to quantify the pharmacokinetic drug-drug interaction between CsA and nicardipine, amlodipine, and lacidipine. In all, 51 children who received CsA and CCB concomitantly were included.

RESULTS:

Dose-normalized CsA trough blood concentrations significantly increased in patients treated with nicardipine and amlodipine, whereas they remained stable in patients treated with lacidipine.

CONCLUSIONS:

Because lacidipine appears to have no effect on CsA exposure, it may be the best option among CCBs for treating high blood pressure caused by CsA in children.

• Authors: Elodie Bernard, Sylvain Goutelle, Yves Bertrand, Nathalie Bleyzac
• Journal: The Annals of pharmacotherapy (Ann Pharmacother) Vol. 48 Issue 12 Pg. 1580-4 (Dec 2014) ISSN: 1542-6270 [Electronic] United States
• PMID: 25280976 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2014.

Chemical References

• Calcium Channel Blockers
• Dihydropyridines
• Immunosuppressive Agents
• Amlodipine
• lacidipine
• Cyclosporine
• Nicardipine

Topics

• Adolescent
• Amlodipine (pharmacokinetics, therapeutic use)
• Calcium Channel Blockers (pharmacokinetics, therapeutic use)
• Child
• Child, Preschool
• Cyclosporine (adverse effects, pharmacokinetics)
• Dihydropyridines (pharmacokinetics, therapeutic use)
• Drug Interactions
• Female
• Hematopoietic Stem Cell Transplantation
• Humans
• Hypertension (chemically induced, drug therapy)
• Immunosuppressive Agents (adverse effects, pharmacokinetics)
• Infant
• Male
• Nicardipine (pharmacokinetics, therapeutic use)
• Retrospective Studies