Date of Award

Fall 1994

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering - (M.S.)

Department

Biomedical Engineering Committee

First Advisor

Arthur B. Ritter

Second Advisor

David S. Kristol

Third Advisor

Stanley S. Reisman

Abstract

The liver is the major organ where chemical breakdown of organic and inorganic compounds takes place. A pharmacokinetic heterogeneous model was developed for the local anesthetic and antiarrhythmic drug lidocaine. It was assumed that transport and elimination of lidocaine and its metabolites are linear with concentration. Simulations were done using VisSim software on a 486 based personal computer to obtain concentration profiles for hepatic clearance and for step input of the drug and its metabolites. It was found that the rate of uptake and rate of breakdown were 0.48 min-1 and 0.49 min-1 respectively for lidocaine. The results are consistent with published data. Similar simulations were done for the lidocaine metabolites MEGX and 3-OHLID.

The same heterogeneous model was used with appropriate changes to include cellular inactivation of the drug and urine output in order to model another antiarrthymic drug, procainamide. Simulations were done for hepatic clearance and for bolus (impulse) input to the model. The rate of uptake and rate of release for procainamide were found to be 9.35 min-1. The rate of breakdown and urine output were 0.0053 min-1 and 0.0013 min-1 respectively.Finally, a parameter sensitivity study was done for both lidocaine and its metabolites and procainamide in order to determine sensitivity of the model to the parameters used. The maximum values of rate constants for which the model can operate in stable range were determined.

Finally, a parameter sensitivity study was done for both lidocaine and its metabolites and procainamide in order to determine sensitivity of the model to the parameters used. The maximum values of rate constants for which the model can operate in stable range were determined.

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