Bioavailability

Biopharmaceutics and pharmacokinetics, Bioavailability

1. BIOAVAILABILITY Dept. Of Pharmaceutics. SREE DATTHA INSTITUTE OF PHARMACY Sheriguda , Ibrahimpatnam , Telangana, 501510. PRESENTED BY MOHAMMED AFREEN (16U21R0017 ) Under the Guidance of Asst. Professor Naga Chandrika M. Pharm SREE DATTHA INSTITUTE OF PHARMACY 1

2. CONTENT SREE DATTHA INSTITUTE OF PHARMACY 2 INTRODUCTION OBJECTIVES SREE DATTHA INSTITUTE OF PHARMACY 2

3. INTRODUCTION The therapeutic effectiveness of a drug depends upon the ability of dosage form to deliver the medicament to its site of action at a rate and attribute to elicit the desired pharmacological response. SREE DATTHA INSTITUTE OF PHARMACY 3 BIOAVAILABLE FRACTION F= BIOAVAILABLE DOSE ADMINISTERED DOSE

4. DEFINITION: The proportion of a drug or other substance which enters the circulation when introduced into the body and so is able to have an active effect. The bioavailability of a drug mainly depends on three major factors they are; 1. Pharmaceutical factors : related to physicochemical properties of the drug and characteristics of a dosage from. 2. Patient – Related factors 3. Route of administration SREE DATTHA INSTITUTE OF PHARMACY 4

5. The influence of route of administration on drug’s bioavailability is generally in the following order with few exceptions; SREE DATTHA INSTITUTE OF PHARMACY 5 Parenteral > Oral > Rectal > Topical

6. OBJECTIVES BIOAVAILABILTY STUDIES ARE IMPORTANT IN THE: 1. Primary stages of development. 2. Determination of influence of excipients, patient- related factors and possible interactions. 3. Development of new formulations of existing drugs. 4. Control of quality of a drug product during early stages of marketing. 5. Comparison of availability of a drug substance from different dosage forms. SREE DATTHA INSTITUTE OF PHARMACY 6

7. CONSIDERATION IN BIOAVAILABILTY STUDY DESIGN Bioavailability – Absolute vs. Relative When the systemic bioavailability of drug administered orally is determined in comparison to its intravenous administration, it is called as ABSOLUTE BIOAVAILABILITY. It is denoted by F. When the systemic availability of a drug after oral administration is compare with that of an oral standard of the same drug it is referred RELATIVE or COMPARITIVE BIOAVAILABILITY. It is denoted by Fr. SREE DATTHA INSTITUTE OF PHARMACY 7

8. Single dose vs. Multiple dose studies The dose to be administered for a bioavailability study is determined from preliminary clinical experiments. Single dose bioavailability studies are very common, easy, offer less exposure to drugs and are less tedious. SREE DATTHA INSTITUTE OF PHARMACY 8 MULTIPLE DOSE STUDY

9. Human volunteers-Healthy subjects vs. Patients Ideally, the bioavailability study should be carried out in patients from whom the drug is intended to be used because of apparent advantages - SREE DATTHA INSTITUTE OF PHARMACY 9

10. MEASUREMENT OF BIOAVAILAILITY SREE DATTHA INSTITUTE OF PHARMACY 10

11. Pharmacokinetic methods : These are very widely used and based on the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of drug. Thus, these are indirect methods. Plasma Level – Time Studies : The method is based on assumption that two dosage forms that exhibit superimposable plasma level – time profiles in a group of subjects should result in identical therapeutic activity. The 3 parameters of plasma level – time studies for determining bioavailability are: SREE DATTHA INSTITUTE OF PHARMACY 11

12. 1.Cmax: ( peak plasma concentration ) It is indication of drug is sufficiently absorbed systematically to provide therapeutic response. 2. t max : The peak time that gives an indication of the rate of absorption . 3. AUC : The area under plasma level – time curve that gives a measure of extent of absorption or amount of drug reaches systemic circulation. The extent of bioavailability can be determined by following equations: SREE DATTHA INSTITUTE OF PHARMACY 12 F   Fr   Fr   Fr  

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14. Urinary excretion studies : The method of assessing bioavailability is based on the principle that excretion of unchanged drug is directly proportional to the plasma concentration of drug. The three major parameters examined in urinary excretion data obtained with a single dose study are: SREE DATTHA INSTITUTE OF PHARMACY 14

15. ( d X u/d t)max :(Maximum urinary excretion rate) It is obtained from the peak of plot between rate of excretion versus midpoint time of urine collection period. It’s value increases as the rate of extent of absorption increases. ( t u )max : (time for maximum excretion rate) : It is analogous to the t max of plasma level data. Xu∞ : (cumulative amount of drug excreted in urine) It is related to the AUC of plasma level data and increases as the extent of absorption increase SREE DATTHA INSTITUTE OF PHARMACY 15

16. Pharmacodynamics methods ; Acute Pharmacological Response Method : When bioavailability measurement by pharmacokinetic methods is difficult, inaccurate, or non reproducible, an acute pharmacological effect such as a change in ECG or EEG readings etc. is related to time course of given drug. Disadvantages : The pharmacological response tends to be more variable and accurate correlation between measured response and drug available from formulation is difficult. The observed response may be due to an active metabolite whose concentration is not proportional to concentration of parent drug. SREE DATTHA INSTITUTE OF PHARMACY 16

17. Therapeutic Response Method : Therapeutically the most definite, this method is based on observing the clinical response to a drug formulation given to patients suffering from disease for which it is intended to be used. Draw backs- Quantitation of observed response is too improper to allow for reasonable assessment of relative bioavailability. Bioequivalence studies are usually conducted using a cross over design in which each subject receives each of test dosage forms. Many patients receive more than one drug. SREE DATTHA INSTITUTE OF PHARMACY 17

18. Reference: D.M. BRAHMANKAR , SUNIL B. JAISWAL ‘BIOPHARMACEUTICS AND PHARMACOKINETICS A TREATISE’. SREE DATTHA INSTITUTE OF PHARMACY 18

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