Physico-chemical fundamentals of pharmacokinetics

Absorption, distribution i elimination drugs large measure they influence just his physical-chemical properties.

Solubility in water and in fat
Substances hydrophilic  do well absorb in GIT. Usually too _ does not weigh on plasmatic proteins  and are mostly excreted kidneys. On the contrary substances lipophilic  are bad they absorb in the GIT, but well skin or mucous membranes. Usually more _ weighs on proteins. For excretion must be increased their hydrophilicity metabolism.

Acidobasic properties
Most medicines they are faintly base or acid. So they occur in ionized and non-ionized form. Membranes better they penetrate non-ionized ( lipophilic ) substances, of which the reason is absorption , excretion and transfer between compartments  dependent at pH. For example, in the acidic pH of the stomach they will faintly acid more in non-ionized form, which allows their easier absorption. On the same principle you can acidification of urine _ _ increase ionized share basic substances in the urine, and reduce so their return resorption , that is increase excretion.

Share ionized faction faintly acid describes Henderson-Hasselbalch equation :

$$ pH = pK_A - \ frac {[A^{-} ]}{ AH} $$

Molecular weight and shape molecules
What the smaller and lighter the molecule, the easier diffuses. Dimensions and shape molecules they are decisive even for permeation non-specific pores, e.g. _ at glomerular filtration.

Binding on protein
Custody on protein refers to especially  lipophilic substances , but they can bind and e.g. _  molecules with suitable electric charge . Custody it happens reversible. The problem is that pharmacologically is only effective free faction. For critical circumstances can be amount available binding places reduced and effect medicines unexpectedly will grow.

If there is a bond drugs L on proteins P reversible, can express dissociative constant KD returnable reaction drugs and proteins :

$$ K_D = \ frac {[P][L ]}{ [PL]} $$

For the practical needs is more advantageous operate with time off fractions drugs fU which you can express the following way :

$$ f_U = \ frac {[L ]}{ [L]+[P]} = \ frac {K_D + [L]}{N + K_D + [L]} $$

N is a number binding places on one molecule proteins.

Category:Pharmacology