Chapter 16 - Page 2 - Java 4

Linear Plot of Cp versus Time after a Single Oral Dose Administration
Two Compartment Model
Renal Excretion and Liver Metabolism Models

Comments

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 (fU), GFR, renal blood flow (QR), intrinsic secretion clearance (CLisec) and fraction reabsorbed (fR).

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 100 mg ± Linear system in this example
Absorption rate half-life, t1/2abs Range 0.1 - 24 hr  
Fraction absorbed
F		 Range 0 - 1.0  
Volume of Distribution
V1		 Range 7 - 200+ L Volume of central compartment
k12 Range 0-25+ hr-1 From central to peripheral
k21 Range 0-25+ hr-1 From central to peripheral
Fraction unbound, in blood
fu, b		 Range 0 - 1  
Hepatic Blood Flow
QH		 90 L/hr
Range 60-120 L/hr		 70 Kg adult, Shargel and Yu, 3rd, 1993
Renal Blood Flow
QH		 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
CLint, ub		 0 - 1620+ L/hr Shargel and Yu, 3rd, 1993
Renal Secretion Clearance
CLsec, 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 CLH, CLR and V

Equation 16.2.4 Concencentration versus Time after a single Oral Dose with A, B, C, α, β and ka

where

Equation 16.2.5 A, B, and C for Equation 16.2.4 with α and β calculated from Dose, V1, kel, k12 and k21

Explore flow limited drug behavior by setting CLint somewhat larger (> 200 L/hr) than the hepatic blood flow rate. Change QH, fu and CLint to see which parameters have the greatest influence of half-life. Capacity limited drug behavior can be explored by setting CLint 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 Add Line button.

References

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