Bioavailability.pptx

Lecture Objectives

After completion of lecture, students will be able to:

• Describe bioavailability, bioequivalence, Half-life, Loading & Maintenance

Dose

• Explain why certain drugs have low bioavailability.

• Explain factors affecting bioavailability.

• Describe clinical importance of bioavailability, bioequivalence, Half-life,

Loading & Maintenance Dose

1. Bioavailability, Half - life, Loading & Maintenance Dose Dr. AWAIS IRSHAD

2. Lecture Objectives After completion of lecture, students will be able to: • Describe bioavailability, bioequivalence, Half-life, Loading & Maintenance Do se • Explain why certain drugs have low bioavailability. • Explain factors affecting bioavailability. • Describe clinical importance of bioavailability, bioequivalence, Half-life, Loading & Maintenance Dose

3. B ioavailability The rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action

4. Bio equivalence Absence of a significant difference in the rate and extent to which the active ingredient or active moiety becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.

5. Routes of administration, bioavailability, and general characteristics

6. Blood concentration - time curves illustrating how changes in the rate of absorption and extent of bioavailability can influence both the duration of action and the effectiveness of the same total dose of a drug administered in three different formulations. The dashed line indicates the target concentration (TC) of the drug in the blood.

7. Plasma drug concentration–time curve after oral drug administration

8. Relationship between plasma drug concentration-versus-time profiles for an intravenously administered formulation versus an orally administered formulation. In an absolute bioavailability study, the systemic exposure profile of a drug administered by the oral route (black curve) is compared with that of the drug administered by the intravenous route (green curve)

9. Plasma concentration-time curves depicting bioavailability differences between three preparations of a drug containing the same amount. Note that formulation B is more slowly absorbed than A , and though ultimately both are absorbed to the same extent (area under the curve same), B may not produce therapeutic effect; C is absorbed to a lesser extent— lower bioavailability

10. A. Extent of Absorption Bioavailability variation assumes practical significance for drugs with low safety margin (digoxin) or where dosage needs precise control (oral hypoglycemics, oral anticoagulants). B. First-Pass Elimination Before a drug enters the systemic circulation, it can be metabolized in the gut wall or in the liver. Any reduction in bioavailability can be caused by any of these sites, the overall process is known as ‘ first-pass elimination’ .

11. Dissolution rate is governed by the inherent solubility, particle size, crystal form and other physical properties of the drug. Differences in bioavailability may arise due to variations in disintegration and dissolution rates.

12. Particle size reduction increases the rate of absorption of aspirin (microfine tablets). The amount of griseofulvin and spironolactone in the tablet can be reduced to half if the drug particle is microfine. There is no need to reduce the particle size of freely water soluble drugs, e.g. paracetamol .

13. Factors Affecting Bioavailability • Physicochemical properties of the drug • Route of drug administration • Ionization • Food • Presence of other drugs • Area of absorbing surface • Diseases • First-pass metabolism (Enterohepatic Cycling)

14. Plasma Half-Life • It is the time required for the plasma concentration of a drug to decrease by 50% of its original value . • A drug is almost completely eliminated in four to five half - lives after single administration . Clinical Importance of Plasma Half-Life: • Determine the duration of drug action • Determine the frequency of drug administration • Estimate the time required to reach the steady state

15. Cleara nce • That volume of plasma from which the drug is removed in unit time • Clearance = Rate of elimination / Plasma concentration of the drug • First - Order Kinetics: A constant fraction of the drug in the body is eliminated per unit time. • Zero-order kinetics: A constant amount of a drug in the body is eliminated per unit time. • The rate of elimination is independent of plasma drug concentration,

16. Steady State Concentration • The amount of drug eliminated will equal the amount of drug administered in the dosing interval. • The drug is said to have reached steady st a te or plateau level . • It is attained after approximately 4-5 half-lives .

17. Loading Dose • The loading dose or initial bolus dose of a drug, is used to obtain desired concentrations as rapidly as possible. • Loading dose is given to saturate the tissue stores so it is mainly dependent on ‘ volume of distribution’ . • e . g . the h a lf - life of lignocaine is more th a n 1 hour, so it takes more than 4-6 hours to reach the t a rget concentr a ti o n at st ea d y stat e .

18. Maintenance Dose: A drug dose that is repeated at regular intervals or given as a continuous infusion to maintain a target level in plasma or steady state concentration . Th e dose admi n iste r e d is equ a l to dose e limi n a t e d in a do s ing int e rval.

19. Referenc es: • Katzung BG, Masters SB and Trevor AJ eds, 2018. Basic & clinical pharmacol ogy. • Rosenbaum SE ed, 2016. Basic pharmacokinetics and pharmacodynamics: An integrated textbook and computer simulations. John Wiley & Sons. • Tripathi KD, 2013. Essentials of medical pharmacology. JP Medical Ltd. • Rang And Dale’s Pharmacology ( © 2020, Elsevier ) James M. Ritter, Rod Flower, Graeme Henderson, Et Al,