2. DEFINITION-
● Bio-availability is the rate and extent to which the active
ingredient is absorbed from the drug product and becomes
available at the site of action.
● The dose available to the patient is called bio-available dose
which is often less than the administered dose
● Amount of drug that reached the systemic circulation is
called systemic availability or simply availability.
4. PURPOSE OF BIO-AVAILABILITY STUDIES
● To obtain evidence of therapeutic utility for a new drug entity in the
primary stages of development of suitable dosage form.
● To determine the influence of excipients, patient related factors and
possible interaction with other drug on the efficiency of absorption.
● To develop new formulations from the existing drugs.
● To control the quality of drug product during the early stages of
marketing in order to determine the influence of processing factors,
storage and stability on drug absorption.
● To compare the availability of drug substance from different dosage
forms or from same dosage form produced by different manufacturers.
7. 1. PLASMA DRUG CONCENTRATION -
● Direct and objective way to determine systemic
bio-availability.
● By appropriate blood sampling
Parameters estimated:
1. tmax
2. Cmax
3. AUC
8.
9. tmax
● The time of peak plasma concentration, it corresponds to the time
required to reach maximum drug concentration after drug
administration.
● At tmax peak drug absorption occurs and the rate of absorption is equal
to rate of drug elimination.
● Drug absorption still continues after tmax is reached, but at a slower rate.
● It can be used as an approximate indication of drug absorption rate.
● tmax will be smaller when there is rapid absorption
● Unit- hours or mins
10. Cmax
● Peak plasma drug concentration
● represents maximum plasma drug concentration obtained after oral
administration of drug
● Units - mg/mL; ng/mL
● Used in BE studies as a surrogate measure for the drug bio-availability.
● It is directly proportional to rate of absorption.
11.
12.
13.
14.
15.
16. URINARY DRUG EXCRETION DATA
● Indirect method for estimating bio-availability
● The drug must be excreted in significant quantities as unchanged drug in
urine
● Timely urine samples are collected and the total amount of urinary Drug
excretion must be obtained.
● Parameters estimated-
Du
∞ - cummulative amount of drug excreted in urine
dDu/dt- rate of drug excretion
t∞- The total time for drug to be excreted.
17. Du
∞
● Directly related to the total amount of drug absorbed.
● Urine samples are collected periodically after administration
of a drug product.
● Each urine specimen is analyzed for free drug using a specific
assay
● Curve- Du
∞ Vs time
18.
19. dDu/dt
● Most of the drugs are eliminated by a first-order rate process, the rate of
drug excretion is dependent on the first order elimination rate constant K,
and the concentration of drug in plasma. Cp
● Rate is maximum at point
B and minimum at point
A and C
20. t∞
● Total time for the drug to be excreted.
● Point C is related to total time required after drug administration for the
drug to be absorbed and completely excreted.
● t∞ is a useful parameter in bioequivalence studies that compare several
drug products.
