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)
Equation 16.2.2 Hepatic Clearance according to the Well Stirred Model
|Dose||100 mg ±||Linear system in this example|
|Absorption rate half-life, t1/2abs||Range 0.1 - 24 hr|
|Range 0 - 1.0|
|Volume of Distribution
|Range 7 - 200+ L|
|Hepatic Blood Flow
Range 60-120 L/hr
|70 Kg adult, Shargel and Yu, 3rd, 1993|
|Renal Blood Flow
||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
|0 - 1620+ L/hr||Shargel and Yu, 3rd, 1993|
|Renal Secretion Clearance
|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 Absorption rate constant
Equation 16.2.5 Concencentration versus Time after a single IV Bolus Dose
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.
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