A 25 year old, 60 kg nonsmoker was to start taking theophylline in addition to her inhalation therapy. Recommend an appropriate theophylline dosing regimen (Loading dose, dose and dosing intervals) for this patient from a fast-release oral product and a sustained release oral product to be given every 12 hr. The therapeutic range of theophylline is 10-20 mg/L, and the average theophylline k and Vd in adult nonsmoker are 0.08 hr-1, and 0.45 L/kg, respectively. The bioavailability of oral theophylline is 100%.
For sustained release product, the maintenance dose should be chosen to achieve an average conc within the therapeutic range (e.g. 15mg/L).
The desired conc is 15mg/L.
(the middle of the therapeutic range)
Assuming that the desired maximum and minimum steady state conc are 20mg/L and 10 mg/L, solve for τ to determine the proper dosing interval.
The proper dose is the dose that can achieve maximum conc of 20mg/L when given every τ.
a- For the sustained release product
15 mg/L =
(1) (Dose)
0.08 hr-1x 27L x 12hr
Dose = 388.8 mg every 12 hr
The dosing regimen is 400mg q 12 hr.
a- For the fast release product
Loading dose =15 mg/L x 27 L= 405 mg = 400 mg
10 mg/L = 20 mg/L e-008 hr-1 τ
τ = 8.66 hr = 8 hr
20 mg/L =
(1) (Dose)
27L x (1 -e-008 hr-1 x 8hr)
Dose =255 mg = 250 mg
