[Pharmacokinetics and biotransformation of 3-cyan-2-morpholino-5-(pyrid-4-yl)pyridine (AWD 122-14) in the rat].
A sensitive isocratic HPLC method for the analysis of AWD 122-14 (1) in plasma and urine was developed. The extraction was processed on-line on a short column. The pharmacokinetics of 1 was studied in rats. The plasma concentration-time course was described by an 1-compartment-model. The pharmacokinetic parameters were estimated. The absorption and elimination of 1 are relatively fast. A single oral dose (D = 1 x 10(-5) mol/kg) was rapidly absorbed (absorption rate constant: kI = 6.85 h-1). The elimination rate constant is kE = 1.59 h-1. The absolute bioavailability of a single oral dose equals 11%. In rats 1 is mainly metabolized. Less than 5% of the dose is excreted in the urine as unchanged drug. The chemical structures of 10 of the 12 isolated metabolites were determined using high-resolution mass spectrometry.
Vagaday
M
M
Pharmakologische Forschungsgesellschaft Biopharm GmbH, Berlin.
Kunter
U
U
Labes
D
D
Hagen
V
V
Böhme
B
B
Franke
P
P
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011485:Protein Binding; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet
D002316:Cardiotonic Agents; D009025:Morpholines; D011725:Pyridines; C077469:3-cyano-2-morpholino-5-(pyrid-4-yl)pyridine
Pharmakokinetik und Biotransformation von 3-Cyan-2-morpholino-5-(pyrid-4-yl)pyridin (AWD 122-14) an der Ratte.