Multiple Dosage Regimens

Loading Dose, Repetitive Intravenous injection, Bioavailability

1. Multiple Dosage Regimens Submitted by, Chandon Chakma PHA-16038 Session:2015-16 MBSTU Submitted to, A.H.M. Mazbah Uddin Lecturer, Department of Pharmacy MBSTU Course: Biopharmaceutics & Pharmacokinetics II

2. Loading Dose Loading Dose Amount of drug in the body Bioavailability (F) x Volume of distribution ( V d ) = Amount of drug in the body = Target conc. (C) x Volume of distribution ( V d ) Loading Dose = C x V d F x S

3. Bioavailability Bioavailable dose Administered dose F = Measurement of the relative amount & rate at which , the drug from administered dosage form , reaches the systemic circulation & becomes available at the site of action. Bioavailable fraction ( F ) , refers to the fraction of administered dose that enters the systemic circulation.

4. Types of Bioavailability Absolute Bioavailability :- If the systemic availability of a drug administered orally is determined by doing its comparison with I.V. administration , it is known as absolute bioavailability. F= AUC Extravascular Dose Extravascular Dose Intravenous AUC Intravenous

5. Types of Bioavailability Relative Bioavailability :- If the systemic availability of a drug administered orally is determined by doing its comparison with that of an oral standard of the same drug , it is known as a relative bioavailability. F rel = AUC Extravascular 1 Dose Extravascular 1 Dose Extravascular 2 AUC Extravascular 2

6. Bioequivalence Operationalized as : Compared exposure in terms of AUC and C max of the plasma Conce - - ntration vs time curve C onclude bioequivalence if the confidence for the ration between the formulations lies between 0.8 and 1.25 for both AUC and Cmax . FDA definition : Pharmaceutical equivalents whose rate and extent of ab -sorption are not statistically different when administered to patients or subjects at the same molar dose under sim-ilar experimental conditions.

7. - kt The maximum amount of drug in the body following a single rapid IV injection is equal to the dose of the drug. For a one-compartment open model , the drug will be eliminated according to first-order kinetics. D B = D o e If 𝜏 is equal to the dosage interval , then the amount of drug remaining in the body after several hours can be determined with : D B = D o e -k𝜏 Repetitive Intravenous Injections

8. Repetitive Intravenous Injections The fraction ( ) of the dose remaining in the body is related to the elimination constant and the dosage interval ( 𝜏 )as follows : If 𝜏 is large , will be smaller because DB (the amount of drug remaining in the body) is smaller.  

9. Repetitive Intravenous Injections If the dose D o = 100mg is given by rapid injection every ,then 𝜏 = . After the the D B = 500mg. After the the D B = 150mg. After the the D B = 75mg. After the the D B = 175mg and so on. You will reach equilibrium at which : D max = 200mg and D min = 100mg