Absorption, distribution, metabolism and excretion. relevant to ALL drugs large research/development area frequent cause of failure of treatment failure of compliance failure to achieve effective level produce toxic effects can enhance patient satisfaction with treatment.
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HA <==> H+ + A- B + HCl <==> BH+ + Cl-
[ UI ] [ I ] [ UI ] [ I ]
pKa = 4.5 (a weak acid)
pH = 2
pH = 7.4
0.1 = [ I ]
[ I ] = 9990
100 = [ UI ]
[ UI ] = 100
100.1 = total drug = 10090
i.v injection gives 100% bioavailability.
Calculated from comparison of the area under the curve (AUC) relating plasma concentration to time for iv dosage compared with other route.
Says nothing about effectiveness.
by gut wall
Targeted drugs , antibody-directed
Plasma protein binding; Tissue sequestration
100-fold increase in free pharmacologically
active concentration at site of action.
less toxic/effective materials
more toxic/effective materials
materials with different type of effect or toxicity
contain cytochrome P450
mixed function oxidases
Hydroxylation -CH2CH3 -CH2CH2OH
Oxidation -CH2OH -CHO -COOH
O-de-alkylation -CH2OCH2- -CH2OH
N-de-alkylation -N(CH3)2 -NHCH3
N-oxidation -NH2 -NHOH
Oxidative deamination -CH2CHCH3
-CHCOCH3 + NH3 NH2
all tend to be less lipid soluble and therefore better excreted (less well reabsorbed)
prolongs action of drugs or inhibits action of those biotransformed to active agents (pro-drugs)
Note effect of pH to make more of weak acid drug present in ionised form in alkaline pH therefore re-absorbed less and excreted faster; vica-versa for weak bases.