Pharmacokinetics of miglitol. Absorption, distribution, metabolism, and excretion following administration to rats, dogs, and man.
The absorption, distribution, metabolism, and excretion of miglitol ((2R,3R,4R,5S)-1-(2-hydroxyethyl)-2-(hydroxymethyl)-3,4,5-piperidinet riol, CAS 72432-03-2, BAY m 1099) have been studied following single and repeated administration of non-labelled and radiolabelled (3H, 14C) drug to rats, dogs, and human volunteers via different routes of administration (intravenous, oral, intraduodenal) and at various doses (0.3-450 mg/kg). After intravenous administration, miglitol is excreted rapidly and completely via the renal route. No indication was found for a metabolization of radiolabelled miglitol. The (renal) clearance of miglitol is in the range of the glomerular filtration rate. Miglitol is rapidly eliminated from plasma with apparent elimination half-lives of 0.4-1.8 h. Miglitol is virtually not bound to plasma proteins. After oral administration miglitol is rapidly and at low doses also completely absorbed. At higher doses (> or = 5 mg/kg in rats and dogs, > 50 mg in humans) a saturation of absorption becomes evident. Miglitol is distributed predominantly in the extracellular space. The volumes of distribution are low (0.3-0.8 l/ kg). In rats high concentrations were initially found in the kidneys, the blood and some well-perfused tissues. The permeation across the blood/brain barrier is very low. Elimination from organs and tissues occurs rapidly resulting in very low residual radioactivity in the body 2 days after dosing (< 0.9% of the dose). At this very low concentration level a terminal elimination phase of radioactivity characterized by half-lives of 50-110 h was observed giving rise to a slight tendency for accumulation (accumulation factors < 6) following repeated administration to rats. In pregnant rats [14C]miglitol crossed the placental barrier slowly and to a limited extent. In lactating rats miglitol was found in milk in concentrations similar to those in the maternal plasma.
Ahr
H J
HJ
Bayer AG, Wuppertal, Germany.
Boberg
M
M
Brendel
E
E
Krause
H P
HP
Steinke
W
W
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000284:Administration, Oral; D000818:Animals; D001345:Autoradiography; D001798:Blood Proteins / Q000378:metabolism; D004285:Dogs; D004386:Duodenum; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000737:chemistry; D005260:Female; D005944:Glucosamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D050112:Imino Pyranoses; D007275:Injections, Intravenous; D008297:Male; D008892:Milk / Q000737:chemistry; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity; D014018:Tissue Distribution
D001798:Blood Proteins; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D050112:Imino Pyranoses; C045621:miglitol; D017485:1-Deoxynojirimycin; D005944:Glucosamine