Plasma concentration, tissue distribution and excretion of the prospective cardioprotective agent cis-(-)-2,3,4,4a,5,9b-hexahydro-2,8-dimethyl-1H-pyrido-[4,3-b]indole dihydrochloride in rats.
Pharmacokinetics of cis-(-)-2,3,4,4a,5,9b-hexahydro-2,8-dimethyl- 1H-pyrido-[4,3-b]indole dihydrochloride (Stobadin; in the following briefly called STB), a pharmacologically active stereoisomer of the gamma-carboline carbidine, was studied using a 3H-labelled product. Determination of STB in biological material was based on liquid-liquid extraction from alkaline media into n-heptane. The plasma concentration of STB following i.v. administration to rats was approximated by a biexponential function. An open two-compartment pharmacokinetic model was conferred to the data with the following parameter estimates: terminal elimination half-life 85.6 min, distribution volume at steady state 4.78 l/kg, total body clearance 105.3 ml/min/kg. The systemic availability of orally given STB dihydrochloride in solution was 19.7%. The brain uptake index of STB was 78.2%. Autoradiography in rats injected i.v. showed a heterogenous distribution of the label in the tissues. STB showed strong affinity to the lung tissue and kidneys and was evenly distributed in the cortex and medulla of the latter organ. During 72 h after i.v. administration, 64.6% and 11.0% of the 3H dose was excreted into urine and faeces, respectively, and after oral administration, the excretion was 62.0% and 21.9%, respectively.
Kállay
Z
Z
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Bittererová
J
J
Brejcha
A
A
Faberová
V
V
Bezek
S
S
Trnovec
T
T
D000284:Administration, Oral; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002243:Carbolines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D002243:Carbolines; C100106:dicarbine