Modeling Drug Delivery in the Rhesus Monkey Koula Quirk, RET Fellow 2010 RET Mentor: Dr. Andreas Linninger Department of Bioengineering, University of Illinois at Chicago NSF- RET Program Abstract Abstract Conclusion Drug Delivery Model Method Method References  Dr. Andreas Linninger, Director NSF RET/UIC  Cierra M. Hall, REU 2010  Sukhi Basati, LPPD  NSF Grant CBET EEC Acknowledgements Motivation  Improved precision of drug dosing will reduce risks and side effects  Need to reduce the number of animals used in clinical drug trials  Deepen our understanding of how drugs interact in the body leading to better drug delivery techniques Objective  To construct a one-dimensional mathematical compartmental model of blood flow in the rhesus monkey The way a drug is absorbed, metabolized, distributed, and eliminated by the body is poorly understood. A computational one- dimensional whole body mathematical model, with the organs represented as compartments, or tubes, is presented. Blood flow is simulated through these as blood pressure drops and blood is distributed throughout the body. Method  Computational modeling provides a scientific way to interpret experimental data while reducing the number of animals used.  Designing better reference models can lead to more advanced simulation avenues which are key for education and research.  This will help in deepening our understanding of human physiology. Using Kirchoff’s conservation laws, Darcy’s law, and the Hagen- Poiseuille equation to model blood flow through compartments, or tubes, I constructed a one- dimensional model to simulate blood distribution through the organs, or compartments.  Normal distribution of cardiac output in the unanesthetized, restrained rhesus monkey. Forsyth. J. Appl. Physiol. 25: 1968  Principles of Anatomy and Physiology, 12th ed. – 2009, Tortora and Derrickson Introduction Introduction Figure 1: Main circulatory routes showing arterial and venous systems, shown for reference. Figure 2: General anatomy of a monkey Figure 3: Computational rhesus monkey model (based on rat model developed in LPPD) The first equation below is Darcy's law,Darcy's law the second is the Hagen-Poiseuille equation:Hagen-Poiseuille equation where: F = blood flow (m*s -1 )ms P = pressure (Pa)Pa R = resistance (m -1 ) ν = fluid viscosity(Pa·s)Pas ππ = mathematical constant L = length of tube (m) r = radius of tube (m) Using these formulas, I computed values for organ resistance from blood flow and pressures reported in experimental data. *GI Tract: large intestine, small intestine, cecum, pancreas, spleen, stomach, and sometimes the colon, rectum and esophagus.(Forsyth, 1968) Cardiac Output (L/min)1.086 Mean Arterial Pressure (mmHg)110 Average Weight (kg)4.1 Cardiac Output (L/(kg*min))0.264 Organ Flow Rates: Brain (L/kg*min))0.627 Liver (L/(kg*min))0.282 Kidneys (L/(kg*min))4.808 GI Tract (L/kg*min))0.749 Brain %CO6.5 Liver %CO4.6 Kidneys %CO12.3 GI Tract %CO11 Brain %wt2.8 Liver %wt4.4 Kidneys %wt0.7 GI Tract %wt4.1 Kirchoff’s conservation law, in essence, states that the sum of voltages in a closed circuit is zero. That is, input must equal output, i.e., in this case, blood is conserved. small intestine