Dalyce M Zuk1, Glen J Pearson. 1. Department of Medicine, University of Alberta, Edmonton, AB T6G2B7, Canada. dalycezuk@capitalhealth.ca
Abstract
BACKGROUND: Recent attention has focused on individualizing mycophenolate mofetil therapy via monitoring of mycophenolic acid (MPA) levels to overcome interpatient variability in MPA exposure when standard doses are administered. To our knowledge, no systematic review of the pharmacokinetic data in orthotopic heart transplant recipients has been published to date. OBJECTIVE: The study aimed to systematically review published studies on the MPA target concentration that is effective at preventing rejection in cardiac transplant patients. METHODOLOGY: A search of MEDLINE (January 1996 to July 2008) and EMBASE (January 1980 to July 2008) was conducted for articles describing the relationship between rejection and MPA concentration. RESULTS: The literature search yielded 7 citations for inclusion: 1 prospective, randomized controlled study (level I); 2 prospective, nonrandomized controlled studies (level II-1); 1 well-designed cohort study (level II-2); 2 retrospective cohort studies (level II-3); and 1 case report (level III). CONCLUSIONS: The relationship between MPA levels and rejection cannot be clearly defined based on available evidence. Preliminary evidence suggests limited sampling strategies may be a better predictor of rejection than a single-time point model. Further studies must be conducted on the relationship between the MPA area under the curve, the risk of rejection, and adverse effects to appreciate the value of such strategies.
BACKGROUND: Recent attention has focused on individualizing mycophenolate mofetil therapy via monitoring of mycophenolic acid (MPA) levels to overcome interpatient variability in MPA exposure when standard doses are administered. To our knowledge, no systematic review of the pharmacokinetic data in orthotopic heart transplant recipients has been published to date. OBJECTIVE: The study aimed to systematically review published studies on the MPA target concentration that is effective at preventing rejection in cardiac transplant patients. METHODOLOGY: A search of MEDLINE (January 1996 to July 2008) and EMBASE (January 1980 to July 2008) was conducted for articles describing the relationship between rejection and MPA concentration. RESULTS: The literature search yielded 7 citations for inclusion: 1 prospective, randomized controlled study (level I); 2 prospective, nonrandomized controlled studies (level II-1); 1 well-designed cohort study (level II-2); 2 retrospective cohort studies (level II-3); and 1 case report (level III). CONCLUSIONS: The relationship between MPA levels and rejection cannot be clearly defined based on available evidence. Preliminary evidence suggests limited sampling strategies may be a better predictor of rejection than a single-time point model. Further studies must be conducted on the relationship between the MPA area under the curve, the risk of rejection, and adverse effects to appreciate the value of such strategies.
Authors: Lewis Cooney; Yoon K Loke; Su Golder; Jamie Kirkham; Andrea Jorgensen; Ian Sinha; Daniel Hawcutt Journal: BMC Med Res Methodol Date: 2017-06-02 Impact factor: 4.615