Soares, M (1)(3), Paixao, P (2)(3), Pereira, L M.(2)(3), Barros, C (2), Cabrita J (2)
(1) Universidade Lusofona, Lisbon Portugal (2) Faculdade de Farmacia da Universidade de Lisboa (3) UFNEB - Unidade de Farmacocinetica nutricao e estudos biofarmaceuticos
Cyclosporin is a imunosupressor widely used in renal transplantation in order to prevent halograph rejection. The inter and intra-individual variability associated with it makes difficult to establish a dose regimen adequate for each individual. The aim of this study is to define a populational pharmacokinetic model that allows proper individualization of regimens. To accomplish our goal a group of 100 patients prescribed with neoral formulations were followed in the first two month after transplantation. Whole-blood concentration where collected at the through and determined by RIA methods. Dose, serum creatinine and weight were monitored over time. Height, age and sex were also registered. A one compartment open model with bolus input was used as a simplification to describe drug levels. A previous analysis was performed on each subject using the ADPAT II program in order to define initial estimates for clearance and volume of distribution which were then used in NONMEM V with ADVAN1 and TRANS2 subroutines. Results indicate that time after transplantation (PTT) and body surface area (BSA) significantly influence the clearance and volume of distribution according with the model: Cl = THETA1 + THETA3.PTT + THETA4.BSA Vd = THETA2 + THETA5.PTT Means values for Clearance and volume of distribution were estimated to be 73.5 L/h (CV=30%) and 1050 L (CV=70%) respectively.
Reference: PAGE 10 (2001) Abstr 218 [www.page-meeting.org/?abstract=218]
Poster: poster