Estimation of agitation intensity in the GI tract in humans and dogs based on in vitro/in vivo correlation.
In this study, we assessed the hydrodynamic flow around a dosage form in the GI tract in humans by comparing the characteristics of in vitro and in vivo release of two different types of controlled release acetaminophen (paracetamol) tablets, A and B. The former tablet showed an agitation speed-dependent release at a high speed range (50-100 rpm), whereas the latter showed this characteristic at a low speed range (10-50 rpm). The mean release amount-time profiles of tablets A and B in humans showed biphasic characteristics, and the first phase of the absorption profiles of A and B was close to their in vitro profiles at a paddle speed of 10 rpm. The in vivo profiles were also superimposable on in vitro dissolution curves obtained by the flow-through cell method at a flow rate of 1 mL/min (velocity 0.89 cm/min) or less. These results indicate that the hydrodynamic flow around the dosage forms in the human GI tract could be extremely low. The in vivo release rate of these tablets in dogs was greater than in humans, and was estimated to be equivalent to the release rate determined by the paddle method at 100 rpm. This indicates that a higher agitation intensity in the GI tract in dogs than in humans may be one cause of the discrepancies between humans and dogs in drug absorption studies.
Katori
N
N
Division of Drugs, National Institute of Health Sciences, Tokyo, Japan.
Aoyagi
N
N
Terao
T
T
D000082:Acetaminophen / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000328:Adult; D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004064:Digestive System / Q000378:metabolism*; D004285:Dogs; D005260:Female; D018495:Fluid Shifts / Q000502:physiology*; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012995:Solubility; D013045:Species Specificity
D003692:Delayed-Action Preparations; D000082:Acetaminophen