Two sampling time profiles for the abbreviated estimation  of mycophenolic acid area under the curve in adult  renal transplant recipients treated with mycophenolate  mofetil and concomitant tacrolimus.
OBJECTIVE
Various studies have revealed that mycophenolic acid (MPA) area under the time concentration curve (AUC) may have clinical value in mycophenolate mofetil dose adjustment. As the full AUC measurement is impractical in clinical practice, several abbreviated AUC profiles using pre-dose, and two or three post-dose samples have been proposed; however, the possible use of lower sampling time profiles has an unquestionable practical interest, and the aim of our study was the evaluation of several two-points algorithms using only one post-dose sample.


METHODS
In 60 MPA concentration-time profiles from 37 adult renal transplant patients treated with mycophenolate mofetil and concomitant tacrolimus, the MPA AUC values were estimated using the three sampling time algorithm (pre-dose, one-half and 2 h post-dose)of Pawinski et al. (Clinical Chemistry 48, 2002, 1497), trapezoidal extrapolated procedure according to Hale et al. (Clinical Pharmacology Therapeutics 64, 1998, 672), and two-points algorithm (pre-dose and 2 h post-dose) proposed by David-Neto et al. (Clinical Transplantation 19, 2005, 19).


RESULTS
The AUC values estimated using the algorithm of Pawinski et al. had a very high correlation(r = 0.997, P < 0.001) with the trapezoidal extrapolated AUC results. The estimated AUC values obtained using the two-points algorithm of David-Neto et al. present a high correlation (r = 0.930, P < 0.001), acceptable mean prediction error (+3.3 +/- 1.8%), and a diagnostic efficiency of 94% in the classification of subtherapeutic, therapeutic, and supratherapeutic values, with respect to the three-points algorithm of Pawinskiet al.


CONCLUSIONS
The two sampling time algorithm of David-Neto gave similar results to those of the three-sampling time algorithm of Pawinski, and both, with sampling over 2 h, may be useful for routine MPA AUC estimation in renal transplant recipients with concomitant tacrolimus. Both are unsuitable when unusually unpredictable pharmacokinetics are expected such as with entericcoated formulations.
Tutor-Crespo
M J
MJ
Unidad Monitorización Fármacos, Laboratorio Central, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Hermida
J
J
Romero
R
R
Tutor
J C
JC
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D016559:Tacrolimus / Q000008:administration & dosage*
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus