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

2. 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

3. Dr. Osama A. A. Ahmed3 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)

4. Dr. Osama A. A. Ahmed4 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  g/ml/hr, and the intravenous dose is 11.2  g/ml/hr, caclculate the bioavailability of the oral dose of the drug? F = 4.5  g/ml/hr / 11.2  g/ml/hr = 0.4 or 40%

5. Dr. Osama A. A. Ahmed5 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 C p 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  g of drug per ml. Calculate the apparent volume of distribution? Vd = 300 mg / 8.2  g/ml = 300 mg / 8.2 mg/L = 36.6 L Elimination half life and elimination rate constant Elimination t 1/2 is the time takes for the plasma drug conc. to fall by one half Elimination rate constant (K el ) is the fractional rate of drug removal per unit time e.g. K el = 0.01 min -1, meaning 1 % per minute K el = 0.693/ t 1/2 Example: Page 327