Measurement of bioavailability

• Bioavailability is measured using pharmacokinetic and pharmacodynamic methods to assess the extent and rate of drug absorption.

A) Pharmacokinetic Measurement

• Pharmacokinetic methods analyze drug concentration in the body over time to determine how much reaches systemic circulation.

• The two main approaches are:

1) Plasma Level-Time Study

• This method measures drug concentration in blood plasma at different time points after administration.

• Process:

1.        Drug Administration – Given via a non-IV (e.g., oral) or IV route (reference).

2.        Blood Sampling – Collected at fixed intervals to track absorption, distribution, and elimination.

3.        Drug Concentration Analysis – Measured using HPLC, mass spectrometry, or immunoassays.

4.        Data Analysis – Generates a plasma concentration-time curve, determining:

• AUC (Area Under the Curve) – Total drug exposure.

• Cmax (Peak Plasma Concentration) – Maximum drug level in plasma.

• Tmax (Time to Cmax) – Time taken to reach peak concentration.

2) Urinary Excretion Study

• Used for drugs primarily excreted unchanged in urine.

• Process:

1.        Drug Administration – Given via non-IV or IV routes.

2.        Urine Collection – Samples taken at specific time intervals.

3.        Drug Concentration Analysis – Using HPLC, mass spectrometry, or immunoassays.

4.        Data Analysis – Calculates:

• Drug excretion per interval.

• Cumulative drug excretion over time.

• Percentage of dose excreted to assess bioavailability.

B) Pharmacodynamic Measurement

• Pharmacodynamic methods evaluate the relationship between drug concentration and its effects, especially when drug levels in blood do not directly correlate with its action.

1) Acute Pharmacological Response

• Measures short-term drug effects after administration.

• Methods:

  • Physiological Changes – E.g., changes in blood pressure, heart rate, pupil dilation.

  • Biochemical Markers – E.g., reduction in blood glucose after an antidiabetic drug.

  • Specific Drug Effects – E.g., receptor occupancy, enzyme inhibition.

2) Therapeutic Response

• Evaluates long-term clinical effectiveness of a drug.

• Methods:

  • Symptom Relief – E.g., pain reduction in chronic pain patients.

  • Disease Progression – E.g., reduced relapses in multiple sclerosis or tumor stabilization in cancer.

  • Survival Rates – E.g., overall survival, progression-free survival in life-threatening conditions.