The influence of gastrointestinal transit on drug absorption in healthy volunteers.
1. The effect of variability of gastric emptying and oro-caecal transit on the absorption of a multicomponent solution of frusemide, atenolol, hydrochlorthiazide and salicylic acid has been studied in six healthy subjects. Each subject was studied on five separate occasions: three times under basal conditions, once following metoclopramide and once following codeine pretreatment in an attempt to speed and slow transit respectively. 2. Inter-subject variability of gastric emptying, oro-caecal transit and the rate and extent of drug absorption was considerable. 3. The absorption of salicylic acid appeared rate-limited by gastric emptying but the rate and extent of frusemide, atenolol and hydrochlorthiazide absorption were unrelated to measures of gastric emptying or oro-caecal transit. 4. Codeine phosphate caused a two-fold delay in oro-caecal transit but did not influence gastric emptying while metoclopramide had no significant effect on either function. 5. Metoclopramide and codeine had no significant effect on the rate or extent of absorption of any of the study drugs. 6. Within the limits of this experiment, oro-caecal transit time did not appear to be an important determinant of frusemide, atenolol, hydrochlorothiazide or salicylic acid absorption. Other factors must account for the observed variability in drug absorption.
Riley
S A
SA
Department of Medicine, Hope Hospital, Manchester.
Sutcliffe
F
F
Kim
M
M
Kapas
M
M
Rowland
M
M
Turnberg
L A
LA
D000284:Administration, Oral; D000328:Adult; D001262:Atenolol / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D003061:Codeine / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005746:Gastric Emptying / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D006852:Hydrochlorothiazide / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008875:Middle Aged; D012459:Salicylates / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D020156:Salicylic Acid
D012459:Salicylates; D006852:Hydrochlorothiazide; D001262:Atenolol; D005665:Furosemide; D008787:Metoclopramide; D020156:Salicylic Acid; D003061:Codeine