Influence of Calcineurin Inhibitor and Sex on Mycophenolic Acid Pharmacokinetics and Adverse Effects Post–Renal Transplant

Tacrolimus or cyclosporine is prescribed with mycophenolic acid posttransplant and contributes to interpatient variability in mycophenolic acid pharmacokinetics and response. Cyclosporine inhibits enterohepatic circulation of the metabolite mycophenolic acid glucuronide, which is not described with...

Full description

Saved in:
Bibliographic Details
Published in:Journal of clinical pharmacology 2019-10, Vol.59 (10), p.1351-1365
Main Authors: Meaney, Calvin J., Sudchada, Patcharaporn, Consiglio, Joseph D., Wilding, Gregory E., Cooper, Louise M., Venuto, Rocco C., Tornatore, Kathleen M.
Format: Article
Language:English
Subjects:
Acids
Antibiotics, Antineoplastic - pharmacokinetics
Area Under Curve
Calcineurin
calcineurin inhibitor
Calcineurin inhibitors
Calcineurin Inhibitors - adverse effects
Cyclosporine - adverse effects
Cyclosporins
Drug Interactions - physiology
enterohepatic circulation
Enterohepatic Circulation - drug effects
Female
Health risk assessment
Humans
Immunosuppressive Agents - adverse effects
Inhibitors
Kidney - drug effects
Kidney transplantation
Kidney Transplantation - methods
Lymphopenia
Lymphopenia - drug therapy
Male
Mathematical models
Middle Aged
Mycophenolate mofetil
Mycophenolic acid
Mycophenolic Acid - pharmacokinetics
Pharmacokinetics
Side effects
Sodium
Statistical analysis
Statistical models
Tacrolimus
Tacrolimus - adverse effects
Transplant Recipients
Variability
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tacrolimus or cyclosporine is prescribed with mycophenolic acid posttransplant and contributes to interpatient variability in mycophenolic acid pharmacokinetics and response. Cyclosporine inhibits enterohepatic circulation of the metabolite mycophenolic acid glucuronide, which is not described with tacrolimus. This study investigated mycophenolic acid pharmacokinetics and adverse effects in stable renal transplant recipients and the association with calcineurin inhibitors, sex, and race. Mycophenolic acid and mycophenolic acid glucuronide area under the concentration‐time curve from 0 to 12 hours (AUC0‐12h) and apparent clearance were determined at steady state in 80 patients receiving cyclosporine with mycophenolate mofetil and 67 patients receiving tacrolimus with mycophenolate sodium. Gastrointestinal adverse effects and hematologic parameters were evaluated. Statistical models evaluated mycophenolic acid pharmacokinetics and adverse effects. Mycophenolic acid AUC0‐12h was 1.70‐fold greater with tacrolimus (68.9 ± 30.9 mg·h/L) relative to cyclosporine (40.8 ± 17.6 mg·h/L); P 
ISSN:0091-2700
1552-4604
1552-4604
DOI:10.1002/jcph.1428