Chapter 16 - Page 2 - Java 1

Linear Plot of Cp versus Time after a Single IV Bolus Dose Administration
One Compartment Model
Renal Excretion and Liver Metabolism Models

Renal clearance can be determined from filtration, secretion and reabsorption parameters according to equation 16.2.1. Each of these rates can be explored further in terms of fraction unbound (f_U), GFR, renal blood flow (Q_R), intrinsic secretion clearance (CLⁱ_sec) and fraction reabsorbed (f_R).

Equation 16.2.1 Renal clearance expanded (Bauer, p 14)

Hepatic clearance can be calculated from three parameters according the well stirred model using equation 16.2.2.

Equation 16.2.2 Hepatic Clearance according to the Well Stirred Model

Table of Parameter Values that might be useful with this simulation

Parameter Value Comment

Dose 500 mg ± Linear system in this example

Absorption rate half-life, t_1/2abs Range 0.1 - 24 hr

Fraction absorbed
F Range 0 - 1.0

Volume of Distribution
V Range 7 - 200+ L

Hepatic Blood Flow
Q_H 90 L/hr
Range 60-120 L/hr 70 Kg adult, Shargel and Yu, 3rd, 1993

Renal Blood Flow
Q_H 72 L/hr
70 Kg adult, Shargel and Yu, 3rd, 1993

Glomerular Filtration Rate, GFR 0 - 7.8+ L/hr Shargel and Yu, 3rd, 1993

Hepatic Intrinsic Clearance
CL_{int, ub} 0 - 1620+ L/hr Shargel and Yu, 3rd, 1993

Renal Secretion Clearance
CL_{sec, ub} 0 - 39.0+ L/hr Shargel and Yu, 3rd, 1993

Fraction Reabsorbed Renal 0 - 1.0

Equations used in this simple pharmacokinetic model.

Equation 16.2.3 Elimination Rate Constant as a function of CL_H, CL_R and V

Equation 16.2.4 Absorption rate constant

Equation 16.2.5 Concencentration versus Time after a single IV Bolus Dose

Explore flow limited drug behavior by setting CL_int somewhat larger (> 200 L/hr) than the hepatic blood flow rate. Change Q_H, fu and CL_int to see which parameters have the greatest influence of half-life. Capacity limited drug behavior can be explored by setting CL_int to a lower value (< 40 L/hr). Explore the effect of V on drug half-life.

Explore the model by changing the parameter(s). Add additional lines with different parameter values using the Plot Line button.

References

Bauer, L.A. 2008 Applied Pharmacokinetics, Second Edition, McGraw-Hill, New York, NY
Burton, M.E., Shaw, L.M., Schentag, J.J., and Evans, W.E. (editors) 2006. Applied Pharmacokinetics & Pharmacodynamics, Principles of Therapeutic Drug Monitoring, Lippincott Williams & Wilkins, p133
Kwon, Y. 2001 Handbook of Essential Pharmacokinetics, Pharmacodynamics, and Drug Metabolism for Industrial Scientists, Kluwer Academic/Plenum Publishers, pp 90-95
Shargel, L., Wu-Pong, S. and Yu, A.B.C. 2005 Applied Biopharmaceutics and Pharmacokinetics, 5th ed., McGraw-Hill, pp 342-343

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Parameter	Value	Comment
Dose	500 mg ±	Linear system in this example
Absorption rate half-life, t_1/2abs	Range 0.1 - 24 hr
Fraction absorbed F	Range 0 - 1.0
Volume of Distribution V	Range 7 - 200+ L
Hepatic Blood Flow Q_H	90 L/hr Range 60-120 L/hr	70 Kg adult, Shargel and Yu, 3rd, 1993
Renal Blood Flow Q_H	72 L/hr	70 Kg adult, Shargel and Yu, 3rd, 1993
Glomerular Filtration Rate, GFR	0 - 7.8+ L/hr	Shargel and Yu, 3rd, 1993
Hepatic Intrinsic Clearance CL_{int, ub}	0 - 1620+ L/hr	Shargel and Yu, 3rd, 1993
Renal Secretion Clearance CL_{sec, ub}	0 - 39.0+ L/hr	Shargel and Yu, 3rd, 1993
Fraction Reabsorbed Renal	0 - 1.0

Chapter 16 - Page 2 - Java 1

Linear Plot of Cp versus Time after a Single IV Bolus Dose Administration One Compartment Model Renal Excretion and Liver Metabolism Models

Linear Plot of Cp versus Time after a Single IV Bolus Dose Administration
One Compartment Model
Renal Excretion and Liver Metabolism Models