Maintenance Dose Rate from Clearance

At steady state, in equals out. Clearance is defined as the volume of plasma completely cleared of drug per unit time, so a clearance of 2.8 L/h holding a concentration of 10 mg/L is removing $2.8 \ imes 10 = 28$ mg every hour, and replacing exactly that much holds the level. Multiply by 24 and you have the 672 mg daily dose a theophylline monograph quotes for a non-smoking adult.

Notice what is absent. The volume of distribution does not appear, and neither does the half-life. The maintenance rate depends only on clearance and the target concentration, which is why two drugs with very different half-lives can need the same daily dose. Half-life governs how long steady state takes to arrive, not where it settles: roughly four to five half-lives, regardless of the dose, which is the reason a loading dose exists at all.

The honest caution is that clearance is the parameter that moves most between patients. Renal or hepatic impairment, cardiac output, age, pregnancy, drug interactions and genetics all shift it, sometimes by a factor of three. This calculation also gives an average rate, not a schedule: giving 672 mg once a day and giving 28 mg an hour by infusion produce the same average concentration but wildly different peaks and troughs, which matters enormously for a drug with a narrow therapeutic window. Dosing intervals are a clinical judgement about peaks and troughs, and this page computes only the average.