Using partition analysis as a facile method to derive net clearances
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Journal articleDate
2022-05-17Department
Pharmaceutical SciencesPermanent link to this record
http://hdl.handle.net/20.500.12613/9712
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http://dx.doi.org/10.1111/cts.13310Abstract
Partition analysis has been described previously by W.W. Cleland to derive net rate constants and simplify the derivation of enzyme kinetic equations. Here, we show that partition analysis can be used to derive elimination and transfer (distribution) net clearances for use in pharmacokinetic models. For elimination clearances, the net clearance approach is exemplified with a mammillary two-compartment model with peripheral elimination, and the established well-stirred and full hepatic clearance models. The intrinsic hepatic clearance associated with an observed average hepatic clearance can be easily calculated with net clearances. Expressions for net transfer clearances are easily derived, including models with explicit membranes (e.g., monolayer permeability and blood–brain barrier models). Together, these approaches can be used to derive equations for physiologically based and hybrid compartmental/ physiologically based models. This tutorial describes how net clearances can be used to derive relationships for simple models as well as increasingly complex models, such as inclusion of active transport and target mediated processes.Citation
Korzekwa K, Yadav J, Nagar S. Using partition analysis as a facile method to derive net clearances. Clin Transl Sci. 2022; 15: 1867-1879. doi:10.1111/cts.13310Citation to related work
Wiley Open AccessHas part
Clinical and Translational Science (CTS), Vol. 15, Iss. 8ADA compliance
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