Clearance Mechanism (Biopharmaceutics)


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Clearance Mechanism (Biopharmaceutics)

  1. 1. Clearance Mechanism Concepts & Pharmacokinetics
  2. 2. Others Hepatic Clearance Renal Clearance Contents 3 4 5 General Clearance2 Introduction1
  3. 3. Introduction:
  4. 4. plasma drug concentration (Penicillin) Elimination Rate Clearance 2 g/mL 30 µg/min 15 ml/min 10 g/mL 150 µg/min 15 ml/min
  5. 5. Clearance models Compartment Model Physiological model Model- Independent Method -Assumes 1st order kinetics
  6. 6. Renal function :
  7. 7. Glomerular filtration rate: is the volume of fluid filtered from the renal (kidney) glomerular capillaries into the Bowman's capsule per unit time.
  8. 8. Creatinine-based approximations of GFR : Creatinine clearance: estimates of creatinine clearance based on the serum creatinine level are used to measure GFR
  9. 9. Creatinine clearance : Creatinine clearance (CCr) is calculated from the creatinine concentration in the collected urine sample.
  10. 10. Hepatic clearance:
  11. 11. Venous equilibration model equation: int int uubH uub CLfQ CLf E  
  12. 12. Drugs can be classified into three types depending on the intrinsic clearance and binding.
  13. 13. Flow limited drugs: Examples include:- lidocaine, propranolol, morphine. High fU • CLint (= CLtotal int) value int int uubH uubH H CLfQ CLfQ CL   
  14. 14. Capacity limited drugs: Examples include:- phenytoin, warfarin, and quinidine. Very low total intrinsic clearance. [fU • CLint << QH].
  15. 15. Other drugs: The three parameters; QH, fU, and CLint are important determinants of drug elimination Examples include:- Theophylline, antipyrine. Between these two extremes. Capacity-limited but binding-insensitive drugs.
  16. 16. Bile Elimination: Large polar molecules (MW > 400)
  17. 17. The mechanisms of transfer of drugs in milk: both active and passive and influenced by the variations of the composition of milk Milk elimination: Danger for the neonate. The percentage of the dose given passing into milk ( 1%-5%)
  18. 18. The determination of drugs in saliva is done to avoid the sampling of blood, could be used in therapeutic control. Salivary elimination: The salivary concentration of liposoluble drugs is the reflection of their plasma concentration in free form. But certain compounds such as iodide and spiramycin, reach salivary concentrations higher than those in plasma.
  19. 19. • Follows passive diffusion ( Non-ionized) • Examples: • Weak acids ( Sulphonamides) • Weak bases ( Thiamine ) • Metals (Iron) Sweat elimination: • For Gases (Anesthetics) • Two types according to solubility. Pulmonary elimination:
  20. 20. • Prostate secretion • Seminal fluid • Vaginal fluid Genital elimination: • Eg: Doxycycline • Alternative route in case of renal failure . Intestinal elimination:
  21. 21. Thank You!