# Multiple Oral - Example Calculations

Question 1. A drug is to be given by multiple oral doses every 8 hr. After consideration of the patient's clinical condition it is decided that the average drug concentrations should be maintained at 30 mg/L. Assume a one compartment linear model applies to this drug in this concentration range. For this dosage form and patient the bioavailability is 0.83 and the absorption rate constant is 2.13 hr-1. The kel and V for this drug in this patient (70.6 kg) are 0.211 hr-1 and 0.54 L/kg, respectively. Calculate the dose that will achieve this average concentration of 30 mg/L.
Question 2. A drug was given by multiple oral doses of 500 mg every 3 hr. Assume a one compartment linear model applies to this drug in this concentration range. For this dosage form and patient the bioavailability is 0.87 and the absorption rate constant is 1.49 hr-1. The half-life and V for this drug in this patient are 4 hr and 37.8 L, respectively. Calculate the average drug concentration.
Question 3. A drug has been given by multiple oral dose of 25 mg every 12 hours. Assume a one compartment linear model applies to this drug in this concentration range. The half-life and V for this drug in this patient (49.8 kg) are 2.7 hr and 1.05 L/kg, respectively. For this dosage form and patient the bioavailability is 0.88. Assume that e-ka • τ approaches 0 and ka >> kel. Calculate the expected Cpaverage, Cpmin value and a 'very' approximate Cpmax value at steady state.

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Some Equations:

Equation 26.1.1 Minimum Drug Concentration at Steady State after Multiple Oral Doses

If e-ka • τ approaches zero

Equation 26.1.2 Minimum Drug Concentration at Steady State after Multiple Oral Doses

If ka >> kel then ka/(ka-kel) approaches 1.

Equation 26.1.3 Minimum Drug Concentration at Steady State after Multiple Oral Doses

Estimate, very approximately, Cpmax

Equation 26.1.4 Approximate value of Cpmax

Equation 26.1.5 Average Drug Concentration, Cp(bar)

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