Comparative scintigraphic assessment of the intragastric distribution and residence of cholestyramine, Carbopol 934P and sucralfate.
It has been demonstrated that orally administered cholestyramine is distributed throughout the stomach and provides prolonged gastric residence via mucoadhesion. Gamma scintigraphy was used to compare the gastric emptying and residence of this resin with two formulations known to exhibit retentive or bioadhesive properties, Carbopol 934P and sucralfate. Fasted normal subjects received a single radiolabelled dose and gastrointestinal transit was monitored for 6 h. The subjects were fed after 4 h to determine the effects of inducing a fed pattern of motility on the retention of the formulations. Initial gastric emptying was similar (Mean T50+/-S.E.M.: cholestyramine=66.93+/-9.39 min; Carbopol=56.57+/-11.96 min; sucralfate=48.33+/-11.07 min; P=0.548: n=10), however, the emptying of cholestyramine slowed beyond 2 h. This resulted in greater residence for cholestyramine (Mean AUC0-6+/-S.E.M. (relative units)=11516+/-686 versus 7657+/-1170 versus 6170+/-998; cholestyramine versus Carbopol versus sucralfate; P=0.004: n=10), with approximately 25% remaining in the stomach at 6 h compared to 3.84 and 2.65% of Carbopol and sucralfate, respectively. Cholestyramine was also distributed widely throughout the stomach whereas Carbopol and sucralfate were concentrated in the body and antrum. Thus, as cholestyramine had a comparable emptying time to Carbopol and sucralfate but greater gastric residence and wider distribution, it could provide a potential mucoadhesive drug delivery system targeting the gastric mucosa for treatment of conditions such as Helicobacter pylori infection.
Jackson
S J
SJ
Department of Surgery, University Hospital, Queen's Medical Centre, NG7 2UH, Nottingham, UK. sarah.jackson@mrc-cam.ac.uk
Bush
D
D
Perkins
A C
AC
D000180:Acrylic Resins; D000328:Adult; D002792:Cholestyramine Resin / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D005746:Gastric Emptying; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011145:Polyvinyls / Q000493:pharmacokinetics*; D013392:Sucralfate / Q000493:pharmacokinetics*; D013667:Technetium
D000180:Acrylic Resins; D011145:Polyvinyls; C006912:carboxypolymethylene; D002792:Cholestyramine Resin; D013392:Sucralfate; D013667:Technetium