Multiple Oral - Example Calculations

Question 1. A drug is to be given by multiple oral doses every 3 hr. After consideration of the patient's clinical condition it is decided that the average drug concentrations should be maintained at 5 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 0.77 and the absorption rate constant is 2.36 hr^-1. The half-life and V for this drug in this patient (99.5 kg) are 4.1 hr and 0.29 L/kg, respectively. Calculate the dose that will achieve this average concentration of 5 mg/L.

Question 2. A drug was given by multiple oral doses of 75 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 0.71 and the absorption rate constant is 0.57 hr^-1. The kel and V for this drug in this patient are 0.181 hr^-1 and 45.3 L, respectively. Calculate the average drug concentration.

Question 3. A drug has been given by multiple oral dose of 30 mg every 8 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 (48.9 kg) are 4.5 hr and 0.9 L/kg, respectively. For this dosage form and patient the bioavailability is 0.64 and the absorption rate constant is 1.23 hr^-1. Calculate the expected Cp_average, Cp_min value and a 'very' approximate Cp_max 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

Cp(min) if exp(-ka*tau) -> zero

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

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

Cp(min) with ka >> kel

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

Estimate, very approximately, Cp_max

Equation 26.1.4 Approximate value of Cp_max

Cp(average)

Equation 26.1.5 Average Drug Concentration, Cp(bar)

Last update: Thu 27 Apr 2006 10:50:20 pm

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