caa a22 4500 475818458 CHVBK 20180406123815.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/s002280000164 doi (NATIONALLICENCE)springer-10.1007/s002280000164 Factors affecting oral cyclosporin disposition after heart transplantation: bootstrap validation of a population pharmacokinetic model [Elektronische Daten] [J. Parke, B. G. Charles] Objective: To determine factors affecting the population pharmacokinetics of oral cyclosporin (CsA) in cardiac allograft recipients during the first 3 weeks after surgery. Methods: Data were obtained from routine trough monitoring and from two extra samples drawn during a dosing interval on a randomly selected day. Whole blood CsA concentrations were assayed using high-performance liquid chromatography (HPLC). Approximately equal numbers of patients were prescribed Sandimmun (SAN) or Neoral (NEO) CsA formulations. Parameter values of a one-compartment kinetic model with first-order absorption and elimination were sought together with the inter-patient and intra-patient variances using the NONMEM program. Results: Improved fits resulted from using the following expression in the model to adjust apparent bioavailability as a function of post-operative day (POD): f=0.2 + 10 × ABS (POD−5)/[(POD + 7) × 60]. The CsA clearance (CL/f ) was found to be influenced by current body weight (WT). There was an absorption lag time of about 35 min with SAN, but zero lag time with NEO. Oral bioavailability (f ) was increased by about 35% with concomitant diltiazem and about 18% with NEO. The CL/f was10% higher during the daytime than at night. The final pharmacokinetic model was validated using 200 bootstrap samples of the original data. Conclusions: Using a validated population modelling approach, it was found that a number of factors influence the pharmacokinetics of CsA during the early post-operative period in cardiac transplant patients. These influences affecting oral bioavailability and clearance may need to be taken into account for maintaining appropriate concentrations of CsA in the bloodstream. Springer-Verlag Berlin Heidelberg, 2000 Key words Cyclosporin nationallicence Heart transplantation nationallicence Population pharmacokinetics nationallicence Parke J. Pharmacy Department, The Prince Charles Hospital, Brisbane, QLD 4032, Australia, AU aut Charles B. G. School of Pharmacy and The Australian Centre for Paediatric Pharmacokinetics, The University of Queensland, Brisbane, QLD 4072, Australia e-mail: Bruce@pharmacy.uq.edu.au Tel.: +61-7-33653194; Fax: +61-7-33651688, AU aut https://doi.org/10.1007/s002280000164 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000164 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Parke J. Pharmacy Department, The Prince Charles Hospital, Brisbane, QLD 4032, Australia, AU aut NATIONALLICENCE 700 1- Charles B. G. School of Pharmacy and The Australian Centre for Paediatric Pharmacokinetics, The University of Queensland, Brisbane, QLD 4072, Australia e-mail: Bruce@pharmacy.uq.edu.au Tel.: +61-7-33653194; Fax: +61-7-33651688, AU aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer