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Bioavailability Measurement of bioavailability

Presented by,

Pradip.L.GhoriM-Pharm 1st yearDept. of Pharmaceutics

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Measurement of bioavailability

Pharmacokinetic methods ( indirect ) 1. Blood analysis

2. Urinary excretion data

Pharmacodynamic methods ( direct ) 1. Acute pharmacological response

2. Therapeutic response

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Blood analysis

Plasma level time studies or The plasma concentration – time curve or blood level curve.

A direct relationship exists concentration of drug at the site of action & concentration of drug in the plasma.

Serial blood samples are taken after drug administration & analyzed for drug concentration.

A typical blood level curve obtained after oral administration of drug.

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Parameters determined

Peak Plasma Concentration (Cmax)

Time of Peak concentration (tmax). Area Under Curve (AUC)

Minimum Effective Concentration (MEC) / Minimum Inhibitory Concentration (MIC).

Maximum Safe Concentration (MSC) / Maximum Safe Dose (MSD).

Duration of action Onset of action. Intensity of action.

Pharmacokinetic parameters

Pharmacodynamics parameters

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AUC or Extent of absorption can be measured by 3 methods…

1.Planimeter Instrument for mechanically measuring the area

2. Cut & weigh method AUC is cut & weighed on analytical balance. The

weight obtained is converted to proper unit by dividing it by the wt of a unit area of same paper.

3. Trapezoidal method

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3. Trapezoidal method

AUC = ½ ( C1 + C2) (t2 – t1) + ½ (C2 + C3) (t3 – t2) +…….

½ (C n-1 + C n ) (tn – tn-1 )

C = Concentration t = time subscript= sample number AUC = Area Under Curve

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Relative bioavailability

F rel = ( AUC) drug . (Dose) standard

(AUC) standard .(Dose) drug

Absolute bioavailability

Fab = (AUC)drug . (Dose) IV

(AUC)IV . (Dose) drug

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Urinary excretion data

The method of determination bioavailability provided that the active ingredient is excreted unchanged in the significant quantity of urine.

The cumulative amount of active drug excreted in urine is directly proportional to extent of systemic drug absorption.

The rate of drug excretion is directly proportional to rate of systemic drug absorption.

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Advantages

Useful when there is lack of sufficiently sensitive analytical techniques to measure concentration of drug in plasma.

Noninvasive method therefore better subject compliance.

Convenience of collecting urine samples in comparison to drawing of blood periodically.

If any case the urine drug concentration is low, assaying of larger sample volume is relatively more.

Direct measurement of bioavailability, both absolute & relative is possible without the necessity of fitting the data to the mathematical model.

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Bioavailability is determined by….

F = ( U ) oral . D IV (U ) IV . D oral

U = Cumulative amt of unchanged drug excreted in urine D IV = IV dose

D oral = oral dose

F = absolute bioavailability

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When equal doses are administered Intravenously & Orally…..

F = ( U ) oral

( U ) IV

F = ( U ) test

( U ) standard

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When drug A was administered IV to a group of volunteers, 80% of the 500mg dose was recovered unchanged in the urine. When the same drug was administered to the same volunteers orally.280 mg was recovered unchanged in urine. What is the absolute bioavailability of Drug A following oral administration.

Absolute bioavailability = (cumulative amt.of drug excreted)sample

(cumulative amt.of drug excreted)IV

= 280 400 = 0.7 or 70%

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Acute pharmacological response

Bioavailability can be determined from the acute pharmacologic effect – time curve as well as from dose response graph.

DISADVANTAGE is that pharmacological response tends to more variable & accurate correlation between the measured response & drug available from the formulation is difficult.

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Therapeutic response

This method is based on the observing the clinical response to a drug formulation given to a patients suffering from disease for which it is intended to be used.

Ex …for anti inflammatory drugs, the reduction in the inflammation is determined.

The major DRAWBACK is …quantification of observed response is too improper to allow for reasonable assessment of relative bioavailability between two dosage forms of a same drug.

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References

“Biopharmaceutics & pharmacokinetics”, D.M. Brahmankar & Sunil B. Jaiswal, Vallabh prakashan.

“Text book of Biopharmaceutics & pharmacokinetics”, Dr.Shobharani R. Hiramath.

“Applied Biopharmaceutics & pharmacokinetics”, Leon Shargel & Andrew B.C.

www.google.com

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Any questions….?

Thank you…….!!!