Pharmacokinetics

- December 23, 2019

Pharmacokinetics means what the body does to the drug through 4 processes which are: absorption, distribution, metabolism, and elimination.

First: Absorption:
means "transfer of the drug from the site of administration to bloodstream."

The rate and extent of absorption depends on environment where drug is absorbed, chemical properties of drug and route of administration.

Ways of absorption:

a) Passive (simple) diffusion is a process in which drug moves from higher concentration region into lower concentration region without a need for carrier or ATP consumed.
b) Facilitated diffusion is like to simple one but a need for protein carrier.
c) Active transport is process in which drug moves from lower concentration region into higher concentration region with need to specific protein carrier and ATP.
d) Endocytosis is a process in which drug is engulfed by cell membrane and transported inside by pinching off drug filled vesicles such as vitamin B12.
e) Exocytosis is a process in which cells secrete their substances out of themselves such as release of norepinephrine.

These figures show various methods of absorption. (Lippincott illustrated reviews of pharmacology).

Factors affecting absorption:

1) There are some factors that are related to drug:

a) Lipid solubility of drug as if it is more lipid soluble or less polar, it will be absorbed easily.
less polar due to absence of polar groups in the structure of the drug such as carboxylic group, amino group, and hydroxyl group.
more lipid soluble increase number of carbon and hydrogen in the structure of drug.

b) Ionization of drug: unionized part of the drug can penetrate the cell membrane and most of drugs are either weak acids or weak bases, so according to the following equations:

HA ⇌ H+ + A− so here in weak acids, uncharged HA can penetrate.
BH+⇌B + H+ so here in weak bases, uncharged B can penetrate.

This part depends on pH of the media where the acidic drug is better absorbed at acidic media such as aspirin is absorbed in stomach while the basic drug is better absorbed at basic media such as diazepum is absorbed in small intestine

c) Nature of the drug: According to physical forms: drug may be gas which can be absorbed rapidly than liquid and solid form. So, volatile gas used as general anesthesia rapidly is rapidly absorbed through pulmonary route.

d) Pharmaceutical preparation.

e) Valency of drug, the drug is absorbed more if valency is decreased as Fe2+ is absorbed quickly than Fe3+.

2) There are some factors that are related to patient:

a) Route of administration.

b) Absorbing surface: as surface area increased, absorption is increased. So, intestine contains many amount of microvili that increase their surface area therefore the absorption process through it is efficient.

c) Systemic circulation: more blood reaching to intestine, more absorption of drug occurs.

d) Presence of other drug: drug may alter rate of absorption of other drug especially drugs that are given orally such as iron which is given with milk decreases absorption.

d) First pass effect: when you are given a drug orally, drug absorbed by GI enters portal circulation and metabolized by liver or gut wall before reaching systematic circulation. For example: a) Gut-wall effect: gastric acidity destroys benzyl penicillin and digestive enzyme destroys insulin so it is recommended that insulin was given intravenously. b) Hepatic effect: drugs extensively metabolized such as nitroglycerine and drugs metabolized to large extent such as propranolol.

Bioavailability:
Fraction of unchanged drug reaching the systemic circulation after any route of administration. For example, if 100 mg of a drug is administered orally and 70 mg is absorbed unchanged, the bioavailability is 0.7 or 70%.
as you see in the following figure ( Lippincott illustrated reviews of pharmacology).