Two 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
(CL^{i}_{sec}) and fraction reabsorbed (f_{R}).

**Equation 16.2.1 Renal clearance expanded (Bauer, p 14)**

**Equation 16.2.2 Hepatic Clearance according to the Well Stirred Model**

Parameter |
Value |
Comment |

Dose | 100 mg ± | Linear system in this example |

Volume of Distribution V _{1} |
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 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 17.2.4 Concencentration versus Time after a single IV Bolus Dose with A, B, α and β calculated from Dose, V _{1}, kel, k12 and k21**

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 Add Line button.

- 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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