Selected bioavailability and pharmacokinetic calculations

1. Selected bioavailability and pharmacokinetic calculations Dr. Osama A. A. Ahmed

2. Selected bioavailability and pharmacokinetic calculations • Biopharmaceutics: the area of study that deals with the properties of drug substances and dosage forms that influence the release of the drug for biologic activity. • Bioavailability: the relative amount of drug from an administered dosage form that enters the systemic circulation. • Pharmacokinetics: the study and characterization of the time course of ADME of drugs. • Plotting and interpreting drug dissolution data (page 322) • Amount of dug bioavailable from a dosage form • Drug’s bioavailability factor (F) represents the decimal percentage of a drug substance available • Example: if the bioavailability factor (F) for a drug substance in a dosage form is 0.60, how many milligrams of drug would be available for absorption from a 100-mg tablet of the drug? • F indicates that only 60% of the drug present in the dosage form is available for absorption • 100mg X 0.60 = 60 mg Dr. Osama A. A. Ahmed

3. Selected bioavailability and pharmacokinetic calculations • Bioequivalent amounts of bioinequivalent dosage forms: • The bioavailability of a given drug substance may vary when in different dosage forms or in the same dosage form but from a different manufacturer. Thus, it may be desired to calculate the equivalent doses for two bioinequivalent products • Example: If the biovailability (F) of digoxin in a 0.25-mg tablet is 0.60 compared to the bioavailability (F) of 0.75 in a digoxin elixir (0.05 mg/ml), calculate the dose of the elixir equivalent to the tablet? • Digoxin biovailable from tablet = 0.25 mg X 0.60 = 0.15 mg • Digoxin biovailable per milliliter of the elixir = 0.05 mg X 0.75 = 0.0375 mg • 0.0375 mg 1 ml • 0.15 mg X ml X = 4 ml • Plotting and interpreting a blood-drug concentration-time curve (Page 323) Dr. Osama A. A. Ahmed

4. Selected bioavailability and pharmacokinetic calculations • The bioavailability of the drug may be determined by comparison of the AUC data for the particular dosage form against the intravenous form. • Example: If the AUC for an oral dose of a drug administered by tablet is 4.5 mg/ml/hr, and the intravenous dose is 11.2 mg/ml/hr, caclculate the bioavailability of the oral dose of the drug? • F = 4.5 mg/ml/hr / 11.2 mg/ml/hr = 0.4 or 40% Dr. Osama A. A. Ahmed

5. Selected bioavailability and pharmacokinetic calculations • Different drugs administered in the same amount will show different volumes of distribution because of distribution characteristics • Where, Vd is volume of distribution, D is the amount of drug in the body, and Cp is the drug’s plasma concentration. • Example: A patient received a single intravenous dose of 300 mg of a drug substance that produced an immediate blood concentration of 8.2 mg of drug per ml. Calculate the apparent volume of distribution? • Vd = 300 mg / 8.2 mg/ml = 300 mg / 8.2 mg/L = 36.6 L • Elimination half life and elimination rate constant • Elimination t1/2 is the time takes for the plasma drug conc. to fall by one half • Elimination rate constant (Kel) is the fractional rate of drug removal per unit time • e.g. Kel = 0.01 min-1, meaning 1 % per minute • Kel = 0.693/ t1/2 • Example: Page 327 Dr. Osama A. A. Ahmed