Evaluation of mycophenolic acid exposure using a limited sampling strategy in renal transplant recipients

Abstract

Background/aims: While there are drug exposure equation models based on limited sampling times for mycophenolate mofetil (MMF), there are few for enteric-coated mycophenolate sodium (EC-MPS), and none that studied Chinese individuals. Our objective is to generate the optimal model equations for estimation of the mycophenolic acid (MPA) area under the plasma concentration-time curve from 0 to 12 h (MPA-AUC(0-12h)) with a limited sampling strategy (LSS) for renal transplant recipients receiving EC-MPS.

Methods: The pharmacokinetics in 31 Chinese renal allograft recipients treated with EC-MPS in combination with tacrolimus and steroids were determined. The model equations were generated by multiple stepwise regression analysis for estimation of the MPA-AUC.

Results: A total of 31 patients with an average age and weight of 37.58 ± 10.9 years and 60.9 ± 10.7 kg, respectively, were included. Mean serum creatinine and glomerular filtration rate were 112.2 ± 17.7 μmol/l and 65.6 ± 14.6 ml/min, respectively. The mean values of AUC(0-12h), pre-dose MPA trough concentration (C0), maximum concentrations (C(max)), and time to reach C(max) (T(max)) were 61.17 ± 26.39 mg·h/l (range 22.9-123.0 mg·h/l), 4.98 ± 4.65 mg/l (range 0.13-20.04 mg/l), 17.54 ± 10.67 mg/l (range 4.08-42.36 mg/l), and 5.0 ± 2.6 h (range 1.0-10.5 h), respectively. The best predictive equation for estimation of MPA-AUC(0-12h) was -3.63 + 8.35 × C4 + 17.04 × C7 + 13.74 × C12 (r(2) = 0.7491), prediction bias (PE%) was 20.9 ± 20.37, and prediction precision (APE%) was 3.66 ± 29.20.

Conclusions: This model provides an effective approach for estimation of full MPA-AUC(0-12h) in Chinese adult renal allograft recipients treated with EC-MPS and tacrolimus.