title: Mycophenolic acid area under the curve values in African American and Caucasian renal transplant patients are comparable.
abstract: The possibility of an effect of ethnicity on the pharmacokinetics of mycophenolic acid, the immunosuppressive metabolite of the prodrug mycophenolate mofetil, was studied over 90 days following renal transplantation in African American (n = 13) and Caucasian patients (n = 20). Since renal dysfunction and time after transplant surgery are two factors known to alter mycophenolic acid pharmacokinetics, two-way analysis of variance of the data at each time point with ethnicity and renal function status as covariates was used to evaluate the possibility of an ethnicity effect on the pharmacokinetic parameters. No statistically significant difference based on ethnicity was detected for the primary pharmacokinetic parameters, abbreviated mycophenolic acid area under the concentration-time curve (MPA AUC), or the predose trough concentration on study days 4, 7, 14, 28, or 90. A statistically significant decrease in MPA AUC and increase in oral apparent clearance were observed in renally impaired patients regardless of ethnicity on days 4, and 4 and 7, respectively. The suggested mechanism for these differences is uremia-induced increased MPA free fraction, leading to a temporary increased clearance for this restrictively cleared drug.
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Pennsylvania Health System, Philadelphia, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Shaw
authors.forename: M
authors.initials: M
authors.lastname: Korecka
authors.forename: S
authors.initials: S
authors.lastname: Aradhye
authors.forename: R
authors.initials: R
authors.lastname: Grossman
authors.forename: L
authors.initials: L
authors.lastname: Bayer
authors.forename: C
authors.initials: C
authors.lastname: Innes
authors.forename: A
authors.initials: A
authors.lastname: Cucciara
authors.forename: C
authors.initials: C
authors.lastname: Barker
authors.forename: A
authors.initials: A
authors.lastname: Naji
authors.forename: A
authors.initials: A
authors.lastname: Nicholls
authors.forename: K
authors.initials: K
authors.lastname: Brayman
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D044383:Black People; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000493:pharmacokinetics*; D044465:White People; D001741:Black or African American
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid