Fraction of theophylline in sustained-release formulation which is absorbed from the large bowel

In a cross-over study of six healthy male volunteers, 500 mg theophylline was administered either as plain tablets or in a sustained release preparation. On each occasion 2 g of non-enteric coated sulphasalazine was administered simultaneously as the time of appearance of sulphapyridine, the product of hydrolysis, in the blood provides an approximation of the oral--caecal transit time. The mean fraction absorbed--time profile was calculated from serial serum concentration measurements of theophylline by a modification of the Wagner-Nelson equation. The mean cumulative fraction of the dose absorbed following administration of the plain tablets was maximal at 3 h i.e. approximately 3 h ahead of the mean oral-caecal transit time, which was 5.9 h. Thus complete absorption occurred in the small intestine. With the sustained--release formulation, approximately only half of the dose was absorbed at the time the medication reached the large bowel i.e. at about 5.4 h. Absorption continued and at least 38% of the administered dose was additionally absorbed over the next 25 h. A reliable lengthened dosage interval is therefore possible with this particular sustained--release formulation.