Contact Info
Department of Applied Mathematics
University of Waterloo
Waterloo, Ontario
Canada N2L 3G1
Phone: 519-888-4567, ext. 32700
Fax: 519-746-4319
PDF files require Adobe Acrobat Reader
MC 6460
Tahmina Akhter | Applied Math, University of Waterloo
Stochastic effects and Fractal Kinetics in the Pharmacokinetics of drug transport
Pharmacokinetics (PK) attempts to model the progression and time evolution of a drug in the human body from administration to the elimination stage. It is the primary quantitative approach used in drug discovery/development (in the pharma industry). The overwhelming majority of PK models are based on equilibrium kinetics with all the reaction kinetics occurring in a well-mixed, homogeneous environment. Of course as is well known, the human body is comprised of heterogeneous media with non-equilibrium chemical kinetics. As a result, the transport processes and reaction mechanisms are often atypical. In this thesis, we apply ideas from stochastic processes and fractal kinetics in order to better capture the time course of a drug through the body when there is spatial and temporal heterogeneity. We discuss the limitations of the Langevin equation and Bourret's approximation and apply Van Kampen's approach to the random differential equations arising from the stochastic formulation of a standard one compartmental pk model. Although one compartment models can produce good fits if a drug disperses rapidly so that equilibrium is achieved (in all tissues) swiftly, in general they are oversimplifications of a complex process. Thus we also extend the two compartmental model Kearns et. al., to incorporate fractal Michaelis Menten kinetics and compare with experimental data from the literature for paclitaxel. Finally, we conclude with a discussion and appraisal of the contribution in the thesis to the field of pharmacokinetics.
Contact Info
Department of Applied Mathematics
University of Waterloo
Waterloo, Ontario
Canada N2L 3G1
Phone: 519-888-4567, ext. 32700
Fax: 519-746-4319
PDF files require Adobe Acrobat Reader
The University of Waterloo acknowledges that much of our work takes place on the traditional territory of the Neutral, Anishinaabeg and Haudenosaunee peoples. Our main campus is situated on the Haldimand Tract, the land granted to the Six Nations that includes six miles on each side of the Grand River. Our active work toward reconciliation takes place across our campuses through research, learning, teaching, and community building, and is co-ordinated within the Office of Indigenous Relations.