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- W1975226543 abstract "Abstract An assay has been developed for 2′-deoxycoformycin (2′-dCF), utilizing the inhibition by the drug of the enzyme adenosine deaminase. This assay is suitable for the detection of 2′-dCF in tissue extracts and biological fluids with a maximal sensitivity of 2 nM. The assay has been used to study the disposition of the drug in foxhounds and to examine the relationship between tissue drug levels and residual tissue adenosine deaminase activity. 2′-dCF was administered intravenously to foxhounds at doses of 0.1, 0.25 and 1.0 mg/kg. The drug disappeared from plasma with α- and β-half times of 12–15 min and 90–120 min respectively. It was cleared into urine at a rate of 2.24 to 3.12 ml/min/kg. Of the administered drug, 54–83 per cent was recovered in the urine and another 10–15 per cent in the tissues at the time of death. Drug accumulation in tissues correlated with the adenosine deaminase content of the tissues. Residual adenosine deaminase activity was under 50 per cent of control activity in all tissues examined after 0.1 mg/kg of 2′-dCF and under 20 per cent of control activity in all tissues after 1.0 mg/kg of 2′-dCF. Rats given 2′-dCF showed initial inhibition of adenosine deaminase with recovery over time in tissues capable of new enzyme synthesis. The variable rates of recovery from enzyme inhibition may be determinants of tissue specific toxicity of 2′-dCF alone or 2′-dCF in combination with adenosine analogs. Dosage schedules are suggested for different clinical objectives." @default.
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- W1975226543 date "1979-06-01" @default.
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- W1975226543 title "Enzyme inhibition titration assay for 2′-deoxycoformycin and its application to the study of the relationship between drug concentration and tissue adenosine deaminase in dogs and rats" @default.
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- W1975226543 doi "https://doi.org/10.1016/0006-2952(79)90636-1" @default.
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