Disposition and clinical pharmacokinetics of microcrystalline theophylline

Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19 +/- 9 min (mean +/- SD). Maximal serum concentrations reached after 100 +/- 30 min were found to be in a rather narrow range: 9.8 +/- 2.5 mg x 1(-1). The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7 +/- 10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.