Pharmacokinetics

By
Faisal Mehboob

Imp terms
The inactive drug, which undergo chemical conversion by metabolic processes
before becoming an active pharmacological agent is term as PRODRUG . e.g.
Methyldopa
An inactive substance given to satisfy the patients symbolic need for drug therapy
is term as Placebo.
A process of drug absorption, distribution, metabolism and excretion is term as
Pharmacokinetics.
The unchanged form of drug reach systemic circulation is term as Bioavailability.
(AUC oral / AUC intravenous * 100)
First order kinetics. Constant fraction of drug is absorb e.g. Following any Route
except IV
Zero-order kinetics. Constant amount (100%) is absorbed after IV
administration.

Dosage
Average dose for an adult to produce a therapeutic effect called
Therapeutic Dose.
Dose which quickly raise the conc. Of drug in plasma to target conc.
Called Loading dose. LD=VD*TC
Dose that maintain steady state of drug in body called maintenance
dose.
MD=CL*TC

Routes of Drug Administration

Enteral. Administration of drug via alimentary canal.
Oral. Advantages. Most convenient, less adv. effect, delivery in circulation is
slow. Disadvantages. Irritation of mucosal surface, impractical in unconscious
condition.
Sublingual. Advantages. Rapid action. Disadvantages. Irritation oral mucosa.
Rectal. Advantages. Drugs irritants for stomach can be use by this route, can be
use for local effect. Disadvantage. Patient may be embraced, Rectal inflammation.

Parenteral. Administration of drug via Injection.

E.g. IV, IM, ID ,SC, IP, IA , IT ,IBM
Advantages. Drug reach the site of action rapidly, can be use in unconscious patient.
Disadvantages. Rapid action can inc adv. effect.

Inhalational. Administration via Respiratory tract.

Advantages. Drugs use as gases, can be rapidly taken or eliminated.
Disadvantages. Special apparatus needed.

Topical. Administration of drug over skin.

Advantages. High local conc. Can be achieved without systemic effect.
Disadvantages. Absorption can occur, especially when there is tissue destruction,
that results in systemic effects.

Factors affecting absorption

Degree of ionization
Chemical nature
Dosage form
Lipid water partition

Factors affecting Distribution

Physical and chemical nature of drug

PH & Pka
Henderson-Hasselbalch Equation pH=Pka + unpronated/pronated
Pka is always constant and is use for drug while pH use for drug.
Low Pka, more drug is acidic.
Acidic drug is more absorbed in acidic medium like stomach and basic drug is
more absorb in basic medium like intestine.
Acidic drug eliminated in basic environment rapidly while basic vice versa.

Ammonium chloride use to make urine pH acidic.

Sodium bicarbonate use to make urine Ph. basic.
The ionic form. If it's an acid, the the deprotonated form is electrically charged
and is expected to be more soluble. If it's a base, then the protonated form is
electrically charged and expected to be more soluble

Drug clearance
Clearance = 1/half life
Clearance = rate of elimination/cl of drug in plasma
Clrenal= rate of eliminationrenal/c
Clliver= rate of eliminationliver/c
Clother=rate of eliminationother/c
Cltotal= CLrenal+ CLliver+CLother

Half life
Time req to change the amount of drug in body by one-half during elimination.
Formula. t1/2 = 0.7 * Vd/ CL

Factors

Dec renal plasma flow

Addition of a 2nd drug
Dec extraction rate

Steady-State Concentration
When rate of drug elimination is equal to the rate of administration and is
expressed as Css= Ro/CLtotal

Redistribution
In addition to crossing the blood-brain barrier (BBB), lipid-soluble
drugs redistribute into fat tissues prior to elimination.
In the case of CNS drugs, the duration of action of an initial dose may
depend more on the redistribution rate than on the half-life. With a
second dose, the blood/fat ratio is less; therefore, the rate of
redistribution is less and the second dose has a longer duration of
action.

Cytochrome p450
General inducers: anticonvulsants (ba rbiturates, p henytoin,
carbamazepine), antibiotics (rifam pin), chronic a lcohol,St. John's
Wort.
General inhibitors: antiulcer medications (cimetidine, omeprazole),
antimicrobials (chloramphenicol, macrolides, ritonavir,ketoconazole),
acute alcohol.

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