Disposition and pharmacokinetics in rats of McN-5707, a potential antidepressant drug
A single 80 mg/kg oral solution dose of McN-5707-/sup 14/C x HBr (trans-6-(2-chlorophenyl)-1,2,3,5,6,10b-hexahydropyrrolo(2,1-a)isoquinoline hydrobromide (1:1)) was administered orally to 40 Wistar rats. Total /sup 14/C concentrations in plasma were high (> 4.5 ..mu..g x equiv/mL) for at least 24 hours after dosing. Unchanged McN-5707 represented < 10% of the total /sup 14/C concs in plasma at 45 min and < 1% at 24 hours after dosing. In the 8 days following dose administration, 23% of the dose was excreted in urine and 70% of the dose was excreted in feces. Analysis (HPLC and TLC) of glusulase treated urine, plasma and fecal samples revealed the presence of multiple metabolites of McN-5707. Unchanged McN-5707 was found only in fecal extracts (2-7% of dose). Single solution doses of McN-5707 x HBr were administered p.o. (20 mg/kg) and i.v. (4 mg/kg) to 39 Wistar rats. Plasma samples were analyzed for McN-5707 using a capillary GC assay. These studies indicated that McN-5707 was well absorbed and extensively metabolized in rats following oral doses.
- Research Organization:
- McNeil Pharmaceutical, Spring House, PA
- OSTI ID:
- 5429129
- Report Number(s):
- CONF-8604222-; TRN: 86-024869
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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ANTIDEPRESSANTS
BIOCHEMICAL REACTION KINETICS
METABOLISM
CARBON 14 COMPOUNDS
EXCRETION
FECES
LIQUID COLUMN CHROMATOGRAPHY
ORAL ADMINISTRATION
RATS
THIN-LAYER CHROMATOGRAPHY
URINE
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CENTRAL NERVOUS SYSTEM AGENTS
CHROMATOGRAPHY
CLEARANCE
DRUGS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
PSYCHOTROPIC DRUGS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
VERTEBRATES
WASTES
550501* - Metabolism- Tracer Techniques