Absorption of [7,8-14C]rac-a-lipoic acid from in situ ligated segments of the gastrointestinal tract of the rat.
rac-a-Lipoic acid (CAS 62-46-4, thioctic acid) is used in human therapy besides the parenteral route also orally in gastric juice soluble galenic formulations in patients suffering from diabetic polyneuropathy which also involves the gastrointestinal tract (GI) tract in about 20% of the diabetic population. In those patients the most common manifestation of the disease due to small intestine dysfunction is diarrhoea as a consequence of which malabsorption of orally administered drugs may result. Due to the importance of the knowledge on absorption characteristics, in preclinical studies on pharmacokinetics the extent of [14C]absorption from a solution of [7,8-14C]rac-a-lipoic acid was investigated in the rat after oral administration by means of comparison of the AUCs from the [14C]plasma concentrations vs those from the intravenous route, yielding 66%. An alternative evaluation by comparison of [14C]material excreted into the urine yielded 93% [14C]absorption. Despite this high and nearly complete absorption, due to the gastroenteral disturbances mentioned above, the question was investigated if the absorption is restricted to only a small area of the GI tract or is extended over a wider area. The latter is expected to make the absorption less sensitive against variations caused by gastrointestinal disturbances due to longer residence times in the GI tract. In order to approach most closely the physiological situation--as compared with different in vitro incubation techniques using isolated GI tract sacs--the in situ technique on 5 ligated areas of the GI tract of the aneasthetized rat (stomach, duodenum, jejunum, ileum, and colon with caecum) was established.(ABSTRACT TRUNCATED AT 250 WORDS)
Peter
G
G
Department of Biochemistry, ASTA Medica AG, Frankfurt/Main, Germany.
Borbe
H O
HO
D000284:Administration, Oral; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
D008063:Thioctic Acid