Effect of the acetylator phenotype on amrinone pharmacokinetics
| Autor: | P Cernak, D P Benziger, S F Kowalsky, E M Wright, J Edelson, R A Hamilton, R M Stroshane |
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| Rok vydání: | 1986 |
| Předmět: |
Adult
Male medicine.medical_specialty Metabolite Urine Pharmacology Amrinone chemistry.chemical_compound Pharmacokinetics Internal medicine medicine Acetylator phenotype Humans Pharmacology (medical) Infusions Intravenous Volunteer Volume of distribution Isoniazid Acetylation Kinetics Endocrinology Phenotype chemistry medicine.drug |
| Zdroj: | Clinical pharmacology and therapeutics. 40(6) |
| ISSN: | 0009-9236 |
| Popis: | Ten healthy male subjects were phenotyped with isoniazid for their acetylator status and then received intravenous amrinone at a dose of 75 mg during a period of 10 minutes. Blood samples were drawn at specified times during a 24-hour period after dosing. Plasma concentrations of amrinone were determined by a specific HPLC method. The plasma concentration data were fitted to a biexponential model by nonlinear regression. The mean apparent first-order elimination t½ for amrinone in the slow acetylators was 4.4 hours, whereas it was 2.0 hours in the fast acetylators (P < 0.05). There was little difference in the volume of distribution at steady state. Clearance was lower in the slow acetylators, 16.6 L/hr, than in the fast acetylators, 37.2 L/hr (P < 0.05). The AUC was higher for the slow acetylators, 4.96 µg · hr · ml−1, than for the fast acetylators, 2.20 µg · hr · ml−1 (P < 0.01). Concentrations of amrinone and its N-acetyl metabolite in the urine from each volunteer were determined. The ratio of N-acetylamrinone to amrinone was calculated and, as expected, the fast acetylators had a higher ratio than did the slow acetylators (P < 0.01). Clinical Pharmacology and Therapeutics (1986) 40, 615–619; doi:10.1038/clpt.1986.235 |
| Databáze: | OpenAIRE |
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