Methods of assessment of Bioavailability


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Methods of assessment of Bioavailability :

Methods of assessment of Bioavailability Presented by: MOSRUR AHMED LASKAR DOCTOR OF PHARMACY(P.B) FIRST YEAR-2016-17 S.G.R.R.I.T.S,Dehradun

Introduction :

Introduction The therapeutic effectiveness of a drug depends upon the ability of the dosage form to deliver the medicament to its site of action at a rate and amount sufficient to elicit the desired pharmacological response. Bioavailability is defined as rate and extent of absorption of unchanged drug from it’s dosage form and become available at the site of action. Bioavailability of a drug from it’s dosage form depends upon 3 major factors: 1.Pharmaceutical factors 2.Patient related factors 3.Route of administration

Methods of assessment of Bioavailability :

Methods of assessment of Bioavailability 1.Pharmacokinetic method : 1.Plasma level-time studies 2.Urinary excretion studies 2.Pharmacodynamic method : 1. Acute pharmacological response 2.Theraputic response

Pharmacokinetic method :

Pharmacokinetic method Widely used and based on assumption that Pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Plasma Level- Time Studies: Most common type of human bioavailability studies. Based on the assumption that there is a direct relationship between the concentration of drug in blood or plasma and the concentration of drug at the site of action. Following the administration of a single dose of a medication, blood samples are drawn at specific time intervals and analyzed for drug content.

Plasma Level- Time Studies:

Plasma Level- Time Studies A profile is constructed showing the concentration of drug in blood at the specific times the samples were taken. Bioavailability (the rate and extent of drug absorption) is generally assessed by the determination of following three parameters. They are.. 1. C max (Peak plasma concentration) 2. t max (time of peak) 3.Area under curve

Plasma Drug Concentration- Time Profile Plasma Drug Concentration- Time Profile :

Plasma Drug Concentration- Time Profile Plasma Drug Concentration- Time Profile A topical plasma concentration- time profile showing pharmacokinetic and pharmacodynamic parameters obtained after oral administration of single dose of a drug.

Peak plasma concentration & Time of peak plasma concentration:

Peak plasma concentration & Time of peak plasma concentration C max (Peak plasma concentration): Maximum concentration of the drug obtained after the administration of single dose of the drug. Expressed in terms of μg /ml or mg/ml t max (Time of peak plasma concentration): Time required to achieve peak concentration of the drug after administration. Gives indication of the rate of absorption. Expressed in terms of hours or minutes.

Area under curve:

Area under curve The area under the plasma level-time curve that gives a measure of the extent of absorption or the amount of drug that reaches the systemic circulation. The extent of bioavailability can be determined by following equations: For signal dose study: For multiple dose study : .

Urinary Excretion Studies:

Urinary Excretion Studies Urinary excretion of unchanged drug is directly proportional to plasma concentration of drug. Thus, even if a drug is excreted to some extent (at least 10 to 20%) in the urine, bioavailability can be determined. eg : Thiazide diuretics, Sulphonamides. Method is useful when there is lack of sufficiently sensitive analytical technique to measure drug concentration. Non-invasive method, so better patient compliance..

Three parameters of urinary excretion :

Three parameters of urinary excretion ( dXu / dt ) max :(Maximum urinary excretion rate): Its value increases as rate and/or extent of absorption increases. Obtained from peak of plot between rate of excretion versus midpoint time of urine collection period.  ( t u ) max :(Time for maximum excretion rate): Its value decreases as absorption rate increases. Analogues of tmax of plasma level data. X u : (Cumulative amount of drug excreted in urine): ( tu )max Related to AUC of plasma level data. It increases as the extent of absorption increases. dXu / dt ) ma

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The extent of bioavailability is calculated from equations: For signal dose For multiple dose

Pharmacodynamic :

Pharmacodynamic These methods are complementary to pharmacokinetic approaches and involve direct measurement of drug effect on a physiological process as a function of time .

Acute Pharmacologic Response :

Acute Pharmacologic Response When bioavailability measurement by pharmacokinetic method is difficult, an acute pharmacologic effect such as effect on pupil diameter, EEG & ECG readings related to time course of drug. Bioavailability can then be determined by construction of pharmacological effect- time curve as well as dose response graphs. Disadvantage: It tends to be more variable. Observed response may be due to an active metabolite whose concentration is not proportional to concentration of parent drug.

Therapeutic Response Method:

Therapeutic Response Method This method based on observing the clinical Response to a drug formulation given to patient suffering from disease. Disadvantage: The major drawbacks of this method is that quantitation of observed response is too improper to allow for reasonable assessment of relative bioavailability between two dosage forms of the same drug. E.g.: Anti-inflammatory drugs. Many patients receive more than one drug

In vitro studies :

In vitro studies Drug dissolution studies may under certain conditions give an indication of drug bioavailability. Dissolution studies are often performed in several test formulations of the same drug. The test formulation that demonstrates the most rapid rate of drug bioavailability in-vitro will generally have the most rapid rate of drug bioavailability in-vivo.

Reference :

Reference Dr. Shobha Rani R. Hiremath . “Text Book Of Biopharmaceutics & Pharmacokinetics”, Pg no. 31-35. V. Venkateshwarlu “ Biopharmaceutics And Pharmacokinetics” Edition 2. Pg no. 388 -418. Brahmankar . D.M, Jaiswal .B. Sunil in “Textbook of Biopharmaceutics and Pharmacokinetics”, Edition –I, Pg no. 322-337. ppt-2810356 [Accessed 24 April 2015].

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