Excipient effects on gastrointestinal transit and drug absorption in beagle dogs.
Previous work has shown that polyethylene glycol 400 (PEG 400) has an accelerating effect on gastrointestinal transit and a modulating influence on drug absorption in humans. The aim of this study was to assess the impact of various excipients, PEG 400, propylene glycol, d-alpha-tocopheryl-polyethylene glycol-1000 succinate (TPGS) and Labrasol on gastrointestinal transit and drug absorption in four beagle dogs using scintigraphy. Each dog received, on five separate occasions, water (control) or a dose of excipient equivalent to 1 g PEG 400, 2 g propylene glycol, 1 g TPGS or 2 g Labrasol dissolved in water and administered in the form of two capsules. The model drugs ampicillin (200mg) and antipyrine (100mg) were co-administered in the capsules. The capsule solutions were radiolabelled with technetium-99m to follow their transit using a dual-headed gamma camera, and blood samples were collected to determine drug pharmacokinetics. On a separate occasion, the drugs were dissolved in saline and given intravenously. The capsules rapidly disintegrated in the stomach liberating their liquid contents. The mean small intestinal transit times for the different treatments (control, PEG 400, propylene glycol, TPGS and Labarasol) were 183, 179, 195, 168 and 154 min, respectively. The corresponding mean absolute oral bioavailability figures were 36, 32, 39, 42 and 32% for ampicillin and 76, 74, 85, 73 and 74% for antipyrine, respectively. The transit and bioavailability data for the excipient treatments were not significantly different from the control. In summary, these excipients, at the doses administered, have limited influence on gastrointestinal transit and drug in beagle dogs.
Department of Pharmaceutics, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Julia D R
JD
Schulze
Erin E
EE
Peters
Ann W
AW
Vickers
J Scott
JS
Staton
Mark D
MD
Coffin
Gary E
GE
Parsons
Abdul W
AW
Basit
D000667:Ampicillin / Q000493:pharmacokinetics; D000818:Animals; D000983:Antipyrine / Q000493:pharmacokinetics; D001682:Biological Availability; D004285:Dogs; D005079:Excipients / Q000494:pharmacology*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005989:Glycerides; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D009930:Organic Chemicals / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D019946:Propylene Glycol / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology
D005079:Excipients; D005989:Glycerides; D009930:Organic Chemicals; D013386:Succinates; C440220:Labrasol; D014810:Vitamin E; D011092:Polyethylene Glycols; D019946:Propylene Glycol; D000667:Ampicillin; C014225:tocophersolan; D000983:Antipyrine