Disposition of [14C]nadolol in dogs with reversible renal impairment induced by uranyl nitrate
| Autor: | S. M. Singhvi, Eric C. Schreiber, Bernard F. Murphy, Louis T. DiFazio, John W. Poutsiaka, Anthony F. Heald |
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| Rok vydání: | 1978 |
| Předmět: |
Male
medicine.medical_specialty Disposition kinetics genetic structures Adrenergic beta-Antagonists Renal function urologic and male genital diseases Toxicology Propanolamines chemistry.chemical_compound Dogs Pharmacokinetics Nadolol Internal medicine medicine Animals Biotransformation Pharmacology Creatinine Disposition Kinetics Linear relationship Endocrinology Uranyl nitrate chemistry Uranyl Nitrate Uranium Kidney Diseases medicine.drug Glomerular Filtration Rate |
| Zdroj: | Toxicology and applied pharmacology. 43(1) |
| ISSN: | 0041-008X |
| Popis: | Disposition of [ 14 C]Nadolol in Dogs with Reversible Renal Impairment Induced by Uranyl Nitrate. Singhvi, S. M., Heald, A. F., Murphy, B. F., DiFazio, L. T., Schreiber, E. C., and Poutsiaka, J. W. (1978). Toxicol. Appl. Pharmacol. 43 , 99–109. A model for studying the effects of renal impairment on the disposition kinetics of a drug has been developed. Intravenous uranyl nitrate (0.5 mg/kg) was used to produce reversible renal impairment in dogs. The disposition kinetics of [ 14 C]nadolol were determined in two unanesthetized bile duct-cannulated beagles before and 3, 7, 11 [one dog], and 18 days after administration of uranyl nitrate. Creatinine was included with the [ 14 C]nadolol dose to permit the estimation of glomerular filtration rate (GFR) in each experiment. Over a period of 3 to 7 days, the GFR in one dog declined to about 25% of normal, followed by complete recovery in 18 days. There was a decrease in the renal clearance of nadolol that paralleled the degree of renal impairment. The disposition half-life of [ 14 C]nadolol increased from a control value of 3.6 to 7.7 hr on Day 7 and decreased to 4.5 hr by Day 18 when the GFR had returned to normal. In the other dog, the disposition half-life of [ 14 C]nadolol increased from a control value of 4.3 to 5.2 hr on Day 7 when the GFR was 64% of normal. In both dogs, a linear relationship was observed between the renal clearance of [ 14 C]nadolol and the GFR. Other pharmacokinetic parameters were also compared at different degrees of renal impairment. Renal impairment had a marked effect on the disposition of nadolol in dogs. |
| Databáze: | OpenAIRE |
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