title: Abbreviated mycophenolic acid AUC from C0, C1, C2, and C4 is preferable in children after renal transplantation on mycophenolate mofetil and tacrolimus therapy.
abstract: In order to allow a similar algorithm to be used for both adults and children on tacrolimus-based and mycophenolate mofetil [MMF, a pro-drug for mycophenolic acid (MPA)]-based immunosuppression, a limited sampling technique from the trough level (C0) and the levels 30 min (C0.5) and 2 h (C2) after intake was to be developed from MPA area under the time-concentration curves (AUC). We retrospectively analyzed 49 full ten-point pharmacokinetic (PK) profiles from 29 pediatric patients on MMF and tacrolimus. We used stepwise multiple regression analysis to calculate limited sampling approaches. Agreement with the AUC was tested by means of Bland and Altman analysis. The correlation between AUC and pre-dose trough concentration was r(2)=0.5188 ( P<0.0001) and between AUC and post-dose trough concentration r(2)=0.6924 ( P<0.0001). The next best correlations were with 2 h (C2, r(2)=0.6711, P<0.0001), 4 h (C4, r(2)=0.6411, P<0.0001), 1.5 h (C1.5, r(2)=0.6344, P<0.0001), and 6 h (C6, r(2)=0.6219, P<0.0001). Three-point estimates at C0, C0.5, and C2 resulted in an acceptable correlation between predicted AUC and AUC from the full profile when we used the formula AUC = 10.01391+3.94791xC0+3.24253xC0.5+1.0108xC2, Pearson's r=0.8996, 95% confidence interval 0.8277-0.9424. However, even better results could be obtained when we used AUC = 8.217+3.163xC0+0.994xC1+1.334xC2+4.183xC4, Pearson's r=0.9456, 95% confidence interval 0.9051-0.9691. Bland and Altman analysis revealed good agreement between AUC predicted from C0, C0.5, and C2 and AUC from the full profile, but was inferior to the four-point approach. Also, the previously reported formula derived for adults was not usable in these patients. A special formula must be used for children. The AUC of MPA can be predicted by limited sampling including C0, C0.5, and C2, while an approach using C0, C1, C2, and C4 is preferable.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada. filler@cheo.on.ca
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D007223:Infant; D016030:Kidney Transplantation / Q000502:physiology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus