Extent of Absorption

More documents

Recommendations

Info

• Good example – metabolism of acetaminophen • Acetaminophen is ordinarily metabolized in the liver by sulfation and glucuronidation to form non-toxic conjugates • These are low capacity pathways, in that the cofactors are available able in only limited concentrations, so these are rate-limiting. • As long as the amount of acetaminophen in the liver is relatively y low, the Phase II pathways can handle the compound, and there is no toxicity. • If the concentration of acetaminophen becomes high enough to overwhelm the capacity of the Phase II pathways, an alternate metabolic pathway, involving Phase I enzymes, becomes active. • The product of the Phase I reaction is a highly reactive quinoneimine, which can form adducts with (bind covalently to) cellular macromolecules, especially proteins. • The binding of the reactive intermediate to cellular macromolecules les destroys the activity of those molecules, and can lead to compromised mised cell function and, ultimately, cell death. ٧٩
• Another good example – metabolism of carbon tetrachloride • Carbon tetrachloride is metabolized by the cytochrome P-450 system in the liver by abstraction of one of the four chlorine atoms. • This results in formation of a highly reactive trichloromethane radical, which initiates a cascade of lipid peroxidation by removing a hydrogen atom from membrane phospholipids. • Damage to the cell membrane causes loss of osmotic integrity, cell swelling and death. ٨٠
Page 1 and 2:
Extent of Absorption The extent of
Page 3 and 4:
٢٠
Page 5 and 6:
Calculation of Bioavailability The
Page 7 and 8:
2. Distribution Distribution is the
Page 9 and 10:
The rate of distribution is indicat
Page 11 and 12: 4. Effect of pH The pH of the blood
Page 13 and 14: Lipid-soluble compounds frequently
Page 15 and 16: The parameter used to reflect the e
Page 17 and 18: when a chemical shows a more extens
Page 19 and 20: Elimination The parameter most comm
Page 21 and 22: The mechanisms of elimination depen
Page 23 and 24: If a chemical undergoes metabolic a
Page 25 and 26: The best measure of the ability of
Page 27 and 28: It is measured from the total amoun
Page 29 and 30: Measurement of dose/AUC for an oral
Page 31 and 32: Summary of Toxicokinetic Parameters
Page 33 and 34: • Example - If you know that 3 mg
Page 35 and 36: • Clearance (Cl( Cl) • A ratio
Page 37 and 38: • Half-life life (t 1/2 1/2 ) •
Page 39 and 40: • Classical toxicokinetics • On
Page 41 and 42: • Two compartment model • The e
Page 43 and 44: Chronic Administration The kinetic
Page 45 and 46: ٦٢
Page 47 and 48: Because the plasma and therefore ti
Page 49 and 50: In simple mathematical terms this m
Page 51 and 52: • Example: Cholinesterase is an e
Page 53 and 54: • Types of Biotransformation Reac
Page 55 and 56: • Anything that affects the activ
Page 57 and 58: • Phase II reactions • Involve
Page 59 and 60: • Acetylation • Replacement of
Page 61: • Significance of Biotransformati
Page 65 and 66: • Induction - an increase in the
Page 67 and 68: • Inhibition - a decrease in the
Page 69 and 70: Factors affecting metabolism 1. Age
Page 71 and 72: 4. Excretion • Excretion • The
show all

Extent of Absorption

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?