A patient is admitted to the clinic in status asthmaticus. Theophylline is administered i.v. and later on an oral dosing regimen is begun. Two oral dosage forms are considered. The first is a fast release tablet and the second is a slow release form. The slow release form may minimize the fluctuation in Cp and allow for less frequent dosing (improving patient compliance). Blood samples are drawn and Cp of theophylline is determined for the first dose of each of the dosage forms.
Useful information:
Therapeutic range is 10 –20 mg/L
Half-life commonly 4 –5 hr
Vd = 0.5 L/Kg
Patient weighs 62.5 Kg
Dose is 400 mg theophylline for each form
1) IV bolus
Cp=11.5 mg/L at 1hr and 6.7 mg/L at 6hr
Calculate ke, t1/2, Vd, and CL
2) Fast release tablet
Cp=9.35 mg/L at 3hr and 6.79 mg/L at 6hr
Calculate the terminal slope. Does this represent ke or ka? If a complete Cp-t profile were available, outline how you could calculate the other rate constant.
3) Slow release tablet
Cp=5.99 mg/L at 6hr and 4.99 mg/L at 12 hr
Calculate the terminal slope. What rate constant does this represent?
Calculate the steady-state peak and trough levels for the IV and slow release dosing regimens. The dosing interval is 8hr and assume the bioavailability for the oral form is F=1. Compare the results.