Limited sampling strategy for mycophenolic acid area under the curve.

Abstract

The immunosuppressive potential of mycophenolate mofetil (MMF), a prodrug for mycophenolic acid, is related to the area under the time-concentration curve (AUC). Full pharmacokinetic (PK) profiles are expensive and cumbersome, and therefore a limited sampling technique would be favorable. The authors retrospectively analyzed 114 full 10-point PK profiles from 61 pediatric patients receiving MMF. Stepwise multiple regression analysis was used to calculate limited sampling approaches. Correlation between AUC and predose trough concentration was r2 = 0.29 (p < 0.0001), and between AUC and postdose trough concentration was r2 = 0.48 (p < 0.0001). The best correlations were with the 2 hours (C2, r2 = 0.59, p < 0.0001), three hours (C3, r2 = 0.52, p < 0.0001), 1.5 hours (C1.5, r2 = 0.50, p < 0.0001), and six hours (C6 r2 = 0.43, p < 0.0001). No combination of any two sampling points resulted in significantly better correlation with AUC, but three-point estimates at C1, C2, and C6 resulted in excellent correlation between predicted AUC and AUC from the full profile when using the formula AUC = 10.75 + (0.98 x C1) + (2.38 x C2) + (4.86 x C6), Pearson r = 0.93, 95% confidence interval 0.89 to 0.95. Bland and Altman analysis revealed good agreement between predicted AUC and AUC from the full profile. The AUC of mycophenolic acid can be predicted by limited sampling including C1, C2, and C6.