Pharmacokinetics and Metabolism

1. Pharmacokinetics and Metabolism
Drug absorption; is the movement of a drug into the bloodstream after administration.
•
Drug distribution; is the disbursement of an unmetabolized drug as it moves through the body's
•
blood and tissues.
Drug metabolism; is the chemical alteration of a drug by the body
•
Drug elimination; is the removal of an administered drug from the body.
•
Volume of distribution: The ratio of the amount of drug in the body to the drug concentration in
•
the plasma or blood.
Clearance: The speed at which the active form of drug leaves the blood/plasma
•
Half-life (t1/2): The time required for the amount of drug in the body or blood to fall by 50%.
•
Bioavailability (F): The fraction (or percentage) of the administered dose of drug that reaches the
•
systemic circulation
Biodisposition: Often used as a synonym for pharmacokinetics; Sometimes used more narrowly
•
to describe elimination
enteral administration: are those in which the drug is absorbed from the gastrointestinal tract.
•
(Oral, sublingual, rectal)
•
Parenteral administration; any non-oral means of administration
•
(intravenous), IM (intramuscular), SQ (under the skin)
•
Others: Inhalation, intranasal, intrathecal (in csf), topical (applied to the skin
•
Bioavailability;
The fraction (or percentage) of the administered dose of drug that reaches the systemic circulation
•
(F)
effective drug concentration;
is the concentration of a drug at the receptor site.
•
In patients, drug concentrations are more readily measured in the blood.
•
Volume of distribution (Vd)
represents the apparent volume into which the drug is distributed to provide the same concentration
•
as it currently is in blood plasma.
It is calculated by the amount of the drug in the body divided by the plasma concentration.
•
Comparison (elimination);
The drug elimination from the body follows 2 di erent systems:
1) Zero order:
a constant amount of drug is eliminated per unit time.
•
only limiting factor is the blood ow to the eliminating organ/tissue.
•
Elimination speed is constant
•
NOT depended on concentration of the drug
•
No Half-Life
•
Ethanol, Phenytoin, aspirin
•
2) First order elimination:
When drug gets metabolized slowly, and the reaction speed depends on the concentration.
•
The speed changes with the concentration
•
The speed of the change is constant (time it takes to eliminate half the dose)
•
Characteristic to most of the medications
•

2. Urine PH effect on elimination
A ect drugs that get excreted in the urine
•
High Urine acidity (Low pH, more H+), helps produce more acidic molecules and decreases their
•
secretion, at the same time having opposite e ect on basic molecules)
1) Weak acidic drugs: Aspirin, Phenobarbital (Luminal, CNS depressant). In case of overdose,
•
Sodium Bicarbonate (basic) transfusion can increase their secretion.
2) Weak basic drugs: Amphetamines, Quinidine, Phencyclidine (Angel dust). There are
•
medication that acidify urine, but this also acidi es blood which can lead to toxicity and is not used
anymore.
Metabolism
is modi cation of a drug.
•
Metabolic reactions convert hydrophobic compounds into more hydrophilic compounds in order for
•
the drug to be excreted by the kidneys.
Polar drugs are easily excreted.
•
1) Phase I: Reduction, Oxidation, Hydrolysis. Produce active metabolites, slows down with aging
•
and contains Cytochrom p450 sytem.
Substances that e ect this system are: Cyclosporins (immunosuppressant), macrolides (antibiotics),
•
antifungals, and grapefruit juice. Warfarin also uses this system.
2) Phase II – Conjugation reactions: Glucuronidation, acetylation, sulfation. Creates inactive
•
metabolites that get secreted via kidneys.
Cytochrome P450 (CYP450) enzymes
are essential for the production of cholesterol, steroids, prostacyclins, and thromboxane.
•
They also are necessary for the detoxi cation of foreign chemicals and the metabolism of drugs.
•
Inducers; İnhibitors
•
Rifampin phenobarbital. Isoniazid
•
Carbamazepine. Azoles
•
Doze calculation
Maintenance dose: Dose of the drug required to replace the eliminated amount.
•
Loading dose: First dose of the drug given to achive necessary concentrations. (When half-life is
•
too high)
Liver/Kidney pathologies maintenance dose can be lower, but not the loading dose.
•
While administrating the drug we have to consider bioavailability. For example if F=50% the dose is
•
doubled.