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[edit | edit source]
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[edit | edit source]
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 :
![{\displaystyle pH=pK_{A}-\ frac{[A^{-}]}{AH}}](https://wikimedia.org/api/rest_v1/media/math/render/svg/9f7200497cb1b6235fe12e14a757f9b9ca45deef)
For more information see Acido -base balance .Molecular weight and shape molecules[edit | edit source]
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[edit | edit source]
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 :
![{\displaystyle K_{D}=\ frac{[P][L]}{[PL]}}](https://wikimedia.org/api/rest_v1/media/math/render/svg/120552b9b7f7a4b7a6e9d230e9d34c4a30aee5c9)
For the practical needs is more advantageous operate with time off fractions drugs fU which you can express the following way :
![{\displaystyle f_{U}=\ frac{[L]}{[L]+[P]}=\ frac{K_{D}+[L]}{N+K_{D}+[L]}}](https://wikimedia.org/api/rest_v1/media/math/render/svg/dedfd509a662ae8d64c8c5359279bde0a825f04b)
N is a number binding places on one molecule proteins .
