Abstract：
:The pharmacokinetics of cyclosporin (CsA) are unusual because of several heterogeneous features which include the presence of more than one conformer, considerable accumulation in erythrocytes and lipoproteins, extensive plasma protein binding, distribution into deep tissues, biliary secretion and hepatic clearance involving a large number of metabolites. In this study, a stochastic compartmental model was developed to describe the heterogeneous elimination kinetics of CsA. This new approach relies on a probabilistic transfer model with a gamma distributed probability intensity coefficient for drug elimination. For comparative purposes both the stochastic model and compartmental deterministic models were fitted to real post infusion data from patients receiving CsA as a 2-hr intravenous infusion. The criteria for selecting the best model showed that the stochastic model, although simpler than the compartmental deterministic models, is more flexible and gives a better fit to the kinetic data of CsA than the compartmental deterministic models. The stochastic model with a random rate intensity coefficient adequately describes the heterogeneous pharmacokinetics of CsA.
journal_name
J Pharmacokinet Pharmacodynjournal_title
Journal of pharmacokinetics and pharmacodynamicsauthors
Claret L,Iliadis A,Macheras Pdoi
10.1023/a:1012295014352keywords:
subject
Has Abstractpub_date
2001-10-01 00:00:00pages
445-63issue
5eissn
1567-567Xissn
1573-8744journal_volume
28pub_type
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