Regional differences in quinine absorption from the undisturbed human colon assessed using a timed release delivery system.
OBJECTIVE
To investigate the regional absorption characteristics of the distal gut using two markers of permeability, quinine (a transcellular probe) and 51CrEDTA (a paracellular probe).


METHODS
The permeability markers were delivered to the undisturbed gastrointestinal tract in 39 healthy volunteers using an oral timed-release delivery vehicle which allowed pulsed release within a particular site of the gut. Site of release was identified using gamma scintigraphy. Absorption of quinine and 51CrEDTA was assessed by measuring the percent excretion in the urine using HPLC and gamma counting respectively. Serial plasma samples allowed time-concentration curves for quinine to be plotted.


RESULTS
There was a significant trend for diminished absorption with more distal delivery of the transcellular probe, quinine, which was: 6.26 +/- 0.87% (small intestine, n = 10); 4.65 +/- 0.93% (ascending colon, n = 16); and 2.59 +/- 0.52% (transverse colon, n = 10) of the ingested dose excreted respectively (p < 0.001). No such gradient was seen with the paracellular marker, 51CrEDTA.


CONCLUSIONS
These results suggest that delayed release formulations should aim for release in the distal small bowel and proximal colon if absorption is to be maximised. Absorption by the transcellular route diminishes in the more distal colon, a fact which has implications for delayed or sustained release formulations.
Hebden
J M
JM
Division of Gastroenterology, University Hospital Nottingham, UK.
Wilson
C G
CG
Spiller
R C
RC
Gilchrist
P J
PJ
Blackshaw
E
E
Frier
M E
ME
Perkins
A C
AC
D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002214:Capsules; D002463:Cell Membrane Permeability; D002614:Chelating Agents / Q000493:pharmacokinetics; D002860:Chromium Radioisotopes; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004492:Edetic Acid / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D011803:Quinine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D000962:Antimalarials; D002214:Capsules; D002614:Chelating Agents; D002860:Chromium Radioisotopes; D003692:Delayed-Action Preparations; D004492:Edetic Acid; D011803:Quinine