Multiple Oral Dose

Plot of Cp versus Time
One Compartment Model

Theophylline has been studied extensively. It has been used commonly and has been the subject of therapeutic drug monitoring (TDM) because of its variable pharmacokinetic parameters and narrow therapeutic window. Theophylline parameter values vary considerably with disease state, enyzme status (drug co-administration or smoker status) and formulation factors. Currently, the therapeutic window ranges from 5 to 20 mg/L whereas earlier a range of 10 to 20 mg/L had been used. Average plasma concentration targets includes values around 10 mg/L or in the range 8 to 15 mg/L (Aminimanizani and Winter, 2004).

Theophylline is marketed in a number of oral dosage forms. Rapid release tablets generally are rapidly and completely absorbed with F close to 1.0 and ka values above 2 hr^-1. The apparent volume of distribution is approximately 0.5 L/Kg (ideal body weight, IBW). Average values of theopylline clearance approximate 0.04 L/Kg/hr (based on IBW). A number of factors can influence this average clearance value. For example; smoking x 1.6, cimetidine co-administration x 0.6, phenytoin co-administration x 1.6, congestive heart failure x 0.5 (depending on status), cystic fibrosis x 1.5, hepatic cirrhosis x 0.5. Considering a 70 Kg (IBW) non-smoker patient the expected V and kel might be 35 L and 0.08 hr^-1. For a patient that smokes the kel would be expected to be approximately 0.125 hr^-1. Try adjusting the parameter values according to these covariates and adjust the dosing regimen to maintain appropriate therapeutic concentrations.

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Multiple Oral Dose

Plot of Cp versus Time One Compartment Model

Plot of Cp versus Time
One Compartment Model