PHARMACOKINETICSPrepared By : Guided By : Parth Patel Dr. Hitesh Jain(M. Pharm Sem.1) M.pharm ,Ph.D

Forwarded By: Dr.U.M. Upadhyay M.pharm ,Ph.D Sigma Institute Of Pharmacy, Vadodara

CONTENTS

Biological Half Life Volume Of Distribution Renal ClearanceTotal Body ClearancePlasma Protein BindingAbsorption Rate Constant Elimination Rate ConstantConclusion

References

PHARMACOKINETICS: Definition: the activity or fate of drugs in the body over a

period of time, including the processes of absorption, distribution, localization in tissues, biotransformation and excretion.

The study of pharmacokinetics involves both experimental and theoretical approaches. The experimental aspect of pharmacokinetics involves the development of biologic sampling techniques, analytical methods for the measurement of drugs and metabolites, and procedures that facilitate data collection and manipulation. The theoretical aspect of pharmacokinetics involves the development of pharmacokinetic models that predict drug disposition after drug administration.

BIOLOGICAL HALF LIFE

Basic Concept And Importance Of Biological Half Life : Half-life is the time taken for the drug concentration to fall to half its original value

ZERO ORDER t1/2 = 0.5Co Ko Co = initial drug concentration Ko = zero order rate constant

VOLUME OF DISTRIBUTION It is defined as the hypothetical volume of body fluid into which a drug is dissolved or

distributed. It is also known as apparent volume of distribution because all parts of the body equilibrated with the drug do not have equal drug concentration.

Drug in circulation distributes to various organs and tissues. When the process of distribution is complete ,different organs and tissues contain varying concentrations of drugs which can be determined by the volume of tissues in which the drug is present.

There is a relationship between concentration of drug in plasma (C)and amount of drug in the body (X).

so = Vd•c where = amount of drug in the body Vd = volume of distribution c = concentration of drug in plasma

amount of drug in the body(X)Apparent volume of distribution(Vd)= plasma drug concentration(C) Vd = X C

RENAL CLEARANCE Renal clearance CLR is defined as the volume of plasma that is cleared of drug per

unit of time through the kidney. Similarly, renal clearance may be defined as a constant fraction of the V D in which the drug is contained that is excreted by the kidney per unit of time. More simply, renal clearance is defined as the urinary drug excretion rate divided by the plasma drug concentration .

An alternative approach to obtaining equation is to consider the mass balance of drug cleared by the kidney and ultimately excreted in the urine. For any drug cleared through the kidney, the rate of the drug passing through kidney (via filtration, reabsorption, and/or active secretion) must equal the rate of drug excreted in the urine.

Rate of drug passing through kidney = rate of drug excreted

CL renal = [(Glomerular filtration rate + Tubular secretion rate) – Tubular reabsorption rate] / Cp

If the renal clearance of the drug is higher than the physiological creatinine clearance (120-130 ml/min), that time we can say that

the tubular secretion helps and contributes the elimination of the drug additionally to filtration.

In early newborns and newborns, glomerular filtration and tubular secretion mechanisms

are immature and not sufficient.

Renal Clearence (CLR) = V x CU

t x CP

V= collected urine volume t= duration to collect the urineCP= plasma concentration of the drugCU= urine concentration of the drug

TOTAL BODY CLEARANCE Total body clearance is a pharmacokinetic term for describing drug

elimination from the body without identifying the mechanism of the process. Total body clearance (body clearance, total body clearance, or cl T) considers the entire body as a single drug-eliminating system from which many unidentified elimination processes may occur. Instead of describing the drug elimination rate in terms of amount of drug removed per time unit (eg, mg/min), Total body clearance is described in terms of volume of fluid clear of drug per time unit (eg, ml/min).

There are several definitions of clearance, which are similarly based on volume of drug removed per unit time. The simplest concept of clearance regards the body as a space that contains a definite volume of body fluid (apparent volume of distribution, V D) in which the drug is dissolved. Total body clearance is defined as the fixed volume of fluid (containing the drug) cleared of drug per unit of time.

The units for clearance are volume/time (eg, ml/min, L/hr). For example, if the cl T of penicillin is 15 ml/min in a patient and penicillin has a V D of 12 L, then from the clearance definition, 15 ml of the 12 L will be cleared of drug per minute.

Alternatively, cl t may be defined as the rate of drug elimination divided by the plasma drug concentration. This definition expresses drug elimination in terms of the volume of plasma eliminated of drug per unit time. This definition is a practical way to calculate clearance based on plasma drug concentration data.

Where d e is the amount of drug eliminated and dd e/dt is the rate of elimination.

PLASMA PROTEIN BINDING

ABSORPTION RATE CONSTANT

ELIMINATION RATE CONSTANT

The elimination rate constant (k) is the fraction of drug in the body which is removed per unit time.

The rate of elimination for most drugs from a tissue or from the body is a first-order process, in which the rate of elimination is dependent on the amount or concentration of drug present. The elimination rate constant, k, is a first-order elimination rate constant with units of time– 1 (eg, hr– 1 or 1/hr). Generally, the parent or active drug is measured in the vascular compartment. Total removal or elimination of the parent drug from this compartment is effected by metabolism (biotransformation) and excretion. The elimination rate constant represents the sum of each of these processes:

References

1. Martin’s physical pharmacy and pharmaceutical sciences ; 6th edition ; by Patrick J.Sinko and Yashveer Singh ; Lippincott Williams and wilkins ; P.No ;258-299

2. Pharmaceutical calculations ;13th edition ;by Howard C.Ansel ;Lippincott Williams and wilkins ; P.No. ;

3. Pharmaceutics; the sciences of dosage form design ; 2nd edition; edited by m.e. Aulton ;Churchill Livingstone; P.No.; 211-289

4. Applied biopharmaceutics and pharmacokinetics ; 5th edition ;by Leon Shargel , Susanna wu pong, Andrew B.C. Yu ; P.No.

5. R brahmankar, s jaiswal