Drug Absorption II Flashcards
Bioavailability [F], describes _______ and is used to _______
- extent of absorption of drug from non-intravenous site of administration
- convert oral doses to intravenous doses and vice-versa
______ used to estimate the rate of absorption
Time to peak and peak plasma concentration [Tmax and Cmax]
Volume of distribution [Vd], describes _______ and is used to _______
- extent of movement of drug throughout various body compartments
- convert a drug dose to a plasma concentration (Cp), i.e., a dilution factor.
factors influencing drug membrane passage
- molecular size
- lipid solubility
- degree of ionization
- concentration gradient
Passive Diffusion: Driven by _______.
-concentration gradient
Aqueous diffusion / filtration:
Limited capacity, channel size varies (generally for drugs of molecular weight < 100-200)
Lipid diffusion:
Favored if drug has high lipid:water partition coefficient, often pH dependent; unionized moiety crosses membrane down concentration gradient. Most important mechanism for majority of drugs with molecular weights of 500-800.
Carrier-Mediated Diffusion.
Many cell membranes contain specialized transporters that regulate entry and exit of important physiologic molecules (sugars amino acids, neurotransmitters), but some also transport foreign chemicals (xenobiotics) including drugs with structural similarity (P-glycoproteins)
Endocytosis:
Substance bound to receptor at cell surface, engulfed by membrane, taken into cell in newly formed vesicle, then released [vitamin B12 and iron]
Exocytosis:
Responsible for secretion of substances from cell. Many neurotransmitters are released from vesicles into extracellular space upon neuronal activation.
Mechanisms for membrane passage
- passive diffusion
- carrier-mediated diffusion
- endocytosis and exocytosis
