Pharmacokinetics Flashcards
pharmacokinetics
- time course of drug action as it relates to the concentration of drug in the plasma
- ADME = Absorption, Distribution, Metabolism, and Excretion
rational therapeutic regimens
- dose
- absorption
- first pass metabolism
- area under the curve
- elimination clearance
- patient compliance
measurement of drug concentration in plasma
-for most drugs, the concentration of drug at its site of action will be related to the concentration of the drug in the systemic circulation. Therefore it can be used to predict therapeutic and/or toxic effects of drugs
Area under the curve clinical significance
- used to compare the amount of drug that reaches the systemic circulation by different routs of administration: bioavailability (F)
- used to compare clearance (CL) of a drug in different individuals after administration of the same dose
- AUC= dose iv/CL or AUC= dose p.o./ (CL/F)
- CLx/CLy = AUCy/AUCx
drug absorption
-the processes by which drugs move from their site of administration to the plasma
processes following oral drug administration
- disintegration of solids and dissolution of drug in fluids of GI tract
- passage of drug across or between cells to reach the systemic circulation
- stomach and small intestine have large surface area for absorption and the drug leaves that area via passive diffusion and drug transporters to the systemic circulation
factors affecting drug absorption
- chemical composition of drug and delivery formulation
- regional differences in blood flow
- transport mechanisms
- permeability characteristics (lipid solubility)
- ion trapping
- non-specific binding
- surface area
types of passive transport
- paracellular transport
- diffusion
- facilitated diffusion
aqueous diffusion
- small molecules
- passive movement driven by concentration gradient
- route may be paracellular or via aqueous pores
lipid diffusion
- passive process
- driven by concentration gradient
- the rate of absorption increases with increasing drug concentration
- the more lipid-soluble, the faster the rate of transport
- lipid soluble drugs cross mbs readily, but they may be poorly soluble in aqueous gut fluids which may limit their absorption
- lipid solubility is affected by the degree of ionization- henderson hasselbach equation
Henderson Hasselbach equation
pKa = pH + log ([AH]/[A-]) or ([BH+]/[B])
-the ionized form is less lipid soluble– A- or BH+
Where in the body are acids/bases best absorbed?
- weak acids- bet in stomach (lower pH)
- weak bases - best at higher pH
- both are well absorbed in the small intestine
Degree of ionization depends on difference between pH and pKa how?
-pH- pKa = -3, Acids = .1, Bases = 99.9
-pH-pKa= -2, acids =1, bases = 99
-pH-pKa = -1, acids = 10, bases =90
-pH-pKa =0, acids =50, bases =50
etc.
ion trapping
- non-ionized forms can diffuse across lipid membranes, so it equilibrates between blood and urine. Then more of the substance can be trapped on one side or the other based on the pH of the compartment
First pass metabolism
some drugs are highly metabolized when they pass through the liver- only a fraction (F) of the absorbed drug reaches the systemic circulation
-intestinal and hepatic