Therapeutic drug monitoring of mycophenolic acid in kidney transplant patients: a abbreviated sampling strategy.
Mycophenolic acid (MPA) levels have demonstrated a good correlation with clinical outcomes, but with great pharmacokinetic variability between patients. Therapeutic drug monitoring (TDM) is recommended to include a 12-hour area under the concentration-time curve (AUC). Since full AUC estimates are not practical for routine monitoring, limited sampling strategies have been suggested. We evaluated MPA pharmacokinetics in 18 stable renal transplant patients receiving mycophenolate mofetil (MMF) as part of their immunosuppressive therapy. The correlation between measured and estimated AUC was assessed using 4 different sparse sampling algorithms. The mean values for C(0) and AUC(0-6h) were 1.8 +/- 1.2 mg/L and 31.1 +/- 14.8 mg*h/L, respectively. The dose-corrected AUC(0-6h) was 35.4 +/- 17.9 mg*h/L. Regarding the single time points, C(0) showed a low correlation with AUC(0-6h) (r(2) = .34); C(1.5), the best correlation (r(2) = .72); and C(3), the worst (r(2) = .07). Sparse sample algorithms used to estimate 12-hour AUC including C(0), C(1), C(2), C(3), C(4), and/or C(6) showed a good correlation with the calculated AUC(0-6) (r(2) = .81-.96). The algorithm that used C(0), C(1), C(2), and C(4) showed the best correlation, but we also found a good correlation (r(2) = .91) with C(0), C(1), and C(2). Based on these results, we have suggested using the 3-point algorithm (C(0), C(1), and C(2)) for MPA TDM in stable renal transplant patients due to the good correlation with drug exposure and better functionality than an algorithm using a 4-hour postdose measurement.
Muller
H
H
Transplant Unit, Higueras Hospital, Talcahuano, Chile. hkmo@cidial.cl
Solari
S
S
Zuniga
C
C
Guerra
I
I
Troncoso
J
J
Ovalle
R
R
Morente
J
J
Pedreros
C
C
D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D012044:Regression Analysis
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone