Detail of "86880-51-5"

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Absolute bioavailability study in the dog with Visacor, a new cardioselective beta blocking drug with intrinsic sympathomimetic activity

Absolute bioavailability study in the dog with Visacor, a new cardioselective beta blocking drug with intrinsic sympathomimetic activity. McAinsh, James; Smith, Robert P.; Ferguson, Robert A. (Pharm. Div., Imp. Chem. Ind. PLC, Cheshire, UK). Eur. J. Drug Metab. Pharmacokinet., 9(2), 129-39 (English) 1984. CODEN: EJDPD2. ISSN: 0398-7639. DOCUMENT TYPE: Journal CA Section: 63 (Pharmaceuticals) Section cross-reference(s): 1 Visacor (ICI 141,292)(I) [86880-51-5] was dosed to 6 beagle dogs in a randomized crossover manner. Five formulations were examd. i.e. a 15 mg/kg i.v. soln., a 50 mg/kg oral soln., and 50, 100 and 200 mg/kg oral powder formulations. The normalized i.v. blood levels of I decayed tri-exponentially with a final phase elimination half-life of about 10 h. The computer fitted data showed the drug to possess a high vol. of distribution for both the central compartment (54% body wt.) and whole body (1384% body wt.) indicating the possibility of a high degree of metab. The drug clearance following i.v. administration was 196 mL/min and the urinary recovery rate of parent drug was 24% (unhydrolyzed) and 40% following hydrolysis with b-glucuronidase. Following oral dosing at 50 mg/kg [as both powder (C) and soln. (B)], 100 (D) and 200 (E) mg/kg (as powder) the systemic blood profiles increased with dose. The mean peak blood level obtained was 61, 51, 81 and 14 mg/mL for formulations, B, C, D and E resp. The systemic bioavailability of I was only about 40%. The areas under the curves increased linearly with dose and the elimination phase half-life was unchanged with dose. The calcd. half-life (7 h) was apparently shorter after oral administration than after i.v. administration (10 h) but this is probably an artifact dependent on the limit of detection of the assay procedure. At 50 mg/kg there were no significant differences in blood profiles or in the urinary excretion of drug between the soln. and powder formulations. However the overall systemic bioavailability was marginally higher with the powder. These observations are consistent for a drug which is cleared by both renal and hepatic elimination processes, which undergoes ''first-class'' metab. on oral dosing and, over the oral dose range studied, obeys linear pharmacokinetics. The significant increase in recovery of parent drug, after hydrolysis of the urine with b-glucuronidase, indicates that the I glucuronide conjugate is present to a significant extent. Also absorption of parent drug from the gastrointestinal tract may not be complete.