Significance of bioavailability Studies

Significance of bioavailability Studies
Importance of bioavailability Studies
Advantages bioavailability Studies

1. IMPORTANCE OF BIOAVAILABILITY STUDIES Presenter: Muhammad Abdul Islam (02332011025) MPhil 1 st semester

2. B ioavailability Bioavailability studies are drug product performance studies used to define the effect of changes in the physicochemical properties of the drug substance, the formulation of the drug and the manufacture process of the drug product (dosage form).

3. Drug Product Performance Drug product performance,in vivo, may be defined as the release of the drug substance from the drug product leading to bioavailability of the drug substance. The assessment of drug product performance is important since bioavailability is related both to the pharmacodynamic response and to adverse events . Thus, performance tests relate the quality of a drug product to clinical safety and efficacy.

4. Continued Drug product performance studies are used in the development of new and generic drug products. Bioavailability is one aspect of drug product quality that links the in vivo performance of a new drug product to the original formulation that was used in clinical safety and efficacy studies.

5. Significance Bioavailability data provide an estimate of the fraction of administered dose that is absorbed into the systemic circulation from the formulation, and provide information about the pharmacokinetics of the drug. Bioavailability studies provide useful information that is important to establish dosage regimens and to support drug labelling, such as distribution and elimination characteristics of the drug.

6. Continued Bioavailability studies provide an indirect information regarding the presystemic and systemic metabolim of the drug and the the role of transporters such as p-glycoproteins. such studies when designed appropriately provide information on the linearity or non-linearity in the pharmacokinectics of the drug and dose proportionally.

7. Continued Bioavailability data play vital roles in regulatory submissions for marketing approval of new and generic drugs throughout the world. Relative bioavailability studies are frequently included in regulatory submissions. For example, the FDA recommends that new drug developers routinely use an oral solution as the reference for a new oral formulation, for the purpose of assessing how formulation impacts bioavailability.

8. Continued Relative bioavailability studies used in drug development include studies to characterize food effects and drug–drug interactions. In a food-effect bioavailability study , oral bioavailability of the drug product given with food (usually a high-fat, high-calorie meal) is compared to oral bioavailability of the drug product given under fasting conditions. The drug product given under fasting conditions is treated as the reference treatment. Drug–drug interaction study determines whether there is an increase or decrease in bioavailability in the presence of the interacting drug. As such, the general drug–drug interaction study design compares drug relative bioavailability with and without (reference treatment) the interacting drug.

9. Continued Relative bioavailability studies are used in developing new formulations of existing immediate-release drug products, such as new modified-release versions or new fixed dose combination formulations. In the case of a new modified-release version , the reference product is the approved immediate-release product. In the case of a new fixed-dose combination , the reference product can be the single-entity drug products administered either separately (ie, three treatments for a fixed-dose combination doublet) or concurrently according to an approved combination regimen (ie, two treatments).

10. Continued Relative bioavailability study designs are also used for bridging formulations during drug development. For example, to evaluate how drug systemic availability from a new premarket formulation compares with that from an existing premarket formulation.

11. Elements of a Bioavailability Study Protocol I. Title A. Principal investigator (study director) B. Project/protocol number and date II. Study objective III. Study design A. Design B. Drug products 1. Test product(s) 2. Reference product C. Dosage regimen

12. Continued D. Sample collection schedule E. Housing/confinement F. Fasting/meals schedule G. Analytical methods IV. Study population A. Subjects B. Subject selection 1 . Medical history 2. Physical examination 3. Laboratory tests

13. Continued C. Inclusion/exclusion criteria 1. Inclusion criteria 2. Exclusion criteria D. Restrictions/prohibitions V. Clinical procedures A. Dosage and drug administration B. Biological sampling schedule and handling procedures C. Activity of subjects

14. Continued VI. Ethical considerations A. Basic principles B. Institutional review board C. Informed consent D. Indications for subject withdrawal E. Adverse reactions and emergency procedures VII. Facilities VIII. Data analysis A. Analytical validation procedure B. Statistical treatment of data IX. Drug accountability X. Appendix