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Keywords:

bicyclam, bio-as, HIV, pharmacokinetics, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Pharmacology & Pharmacy, Virology, bio-assay, HUMAN-IMMUNODEFICIENCY-VIRUS, INHIBITORS, POTENT, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1117 Public Health and Health Services, 3404 Medicinal and biomolecular chemistry

Abstract:

The serum levels of the bicyclam derivative 1,1'-[1,4-phenylenebis(methylene)]-bis-1,4,8,11-etraazacyclotetradecane octahydrochloride dihydrate [SID791 (JM3100)], a potent inhibitor of HIV replication (De Clercq ef al., 1994) were determined in rabbits using two different methods, A method based on the UV-absorption of the Cu-complex of SID791 was used to analyse by HPLC the serum drug concentrations, and an antiviral activity bio-assay was performed to investigate whether the drug in the rabbit serum was in an available active form, After subcutaneous (sc) administration of SID791 to rabbits at 25 mg/kg of body weight, the compound was cleared from the serum in a bi-exponential manner (β1-half-lives: 67 and 69 min; β2-half-lives: 320 and 245 min; distribution volumes: 0.40 and 0.37 l; total body clearance: 0.30 and 0.29 l/h; and AUG: 83.3 and 86.2 h µg/ml, as determined by HPLC and bio-assay, respectively), Thus, very similar kinetic parameters were noted if serum drug concentrations were determined by HPLC analysis or bio-assay, suggesting that in the rabbit serum the drug is present as an antiviral active agent.