[The effect of pretreatment with ranitidine on the pharmacokinetics and gastrointestinal transit of a sustained-release theophylline preparation]

Abstract

A scintigraphic and pharmacokinetic study of the behavior of Bronchoretard forte (theophylline, CAS 58-55-9) was carried out in 8 healthy male volunteers to evaluate the sensitivity of the preparation to changes in gastric pH. The volunteers were pretreated with ranitidine (CAS 66357-35-5) (150 mg b.i.d.) or placebo for three days prior to and on the study day to reduce gastric acidity. The effect of the pretreatment with ranitidine on gastric pH was measured on the day before study begin and the mean pH was significantly increased compared to the placebo (ranitidine pH 2.2 +/- 2.4; placebo pH 1.6 +/- 2.0, p < 0.01 Wilcoxon Signed Rank test). All subjects were pretreated with theophylline for 3 days (500 mg b.i.d.) to achieve steady state. On the study day, the volunteers swallowed two theophylline sustained release capsules, radiolabelled by inclusion of indium-111 micronised Amberlite resin, and the gastrointestinal transit was followed continuously for 14 h using gamma scintigraphy with a further image at 24 h. Blood samples were taken from each subject throughout the study to determine the pharmacokinetic profile of theophylline in the sustained release formulation. No significant differences were found in the gastrointestinal transit of the labelled microparticulates between the data obtained from the group treated with ranitidine and that from the placebo group. Plasma theophylline concentration profiles were identical for the two treatments. These data indicate that the theophylline sustained release formulation is not sensitive to the effects of major changes in gastric H+ concentration.