EFFECT OF PRETREATMENT WITH RANITIDINE ON THE PHARMACOKINETICS AND GASTROINTESTINAL TRANSIT OF A SUSTAINED-RELEASE THEOPHYLLINE PREPARATION

A scintigraphic and pharmacokinetic study of the behaviour of Bronchor etard(R) forte (theophylline, CAS 58-55-9) was carried out in 8 health y male volunteers to evaluate the sensitivity of the preparation to ch anges in gastric pH. The volunteers were pretreated with ranitidine (C AS 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 pretreat ment with ranitidine on gastric pH was measured on the day before stud y begin and the mean pH was significantly increased compared to the pl acebo (ranitidine pH 2.2 +/- 2.4; placebo pH 1.6 +/- 2.0, p < 0.01 Wil coxon Signed Rank test). All subjects were pretreated with theophyllin e 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-lll micronised Amberlite resin, and the gastrointestinal transit was followed continuously for 14 h u sing gamma scintigraphy with a further image at 24 h. Blood samples we re taken from each subject throughout the study to determine the pharm acokinetic profile of theophylline in the sustained release formulatio n. No significant differences were found in the gastrointestinal trans it of the labelled microparticulates between the data obtained from th e group treated with ranitidine and that from the placebo group. Plasm a theophylline concentration profiles were identical for the two treat ments. These data indicate that the theophylline sustained release for mulation is not sensitive to the effects of major changes in gastric H + concentration.