Kinetics of cocaine distribution, elimination, and chronotropic effects
| Autor: | Arthur J. Atkinson, John J. Ambre, Marian W Fischman, May J. Chow, Tsuen Ih Ruo, Dennis J. Bowsher |
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| Rok vydání: | 1985 |
| Předmět: |
Adult
Male Chronotropic medicine.medical_specialty Time Factors Pharmacology Kidney Cocaine Pharmacokinetics Heart Rate Internal medicine Heart rate medicine Humans Distribution (pharmacology) Pharmacology (medical) Volume of distribution Chemistry Half-life Kidney metabolism Kinetics Endocrinology Injections Intravenous Reflex Female Half-Life |
| Zdroj: | Clinical Pharmacology and Therapeutics. 38:318-324 |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1038/clpt.1985.179 |
| Popis: | The pharmacokinetics of cocaine were studied in five subjects with histories of drug abuse who were otherwise healthy. A two-compartment system was used to model the distribution kinetics of the drug. The steady-state volume of distribution averaged 131.8 L or 1.96 L/kg, elimination clearance was 2.10 L/min, and the t 1/2 was 48 minutes. Cocaine concentrations in a hypothetic biophase were estimated to correlate the chronotropic effects of this drug with its pharmacokinetics. The experimentally determined kinetic parameters indicate that the peak chronotropic effect would occur 7.3 minutes after intravenous bolus injection of cocaine, and that biophase cocaine concentrations would initially accelerate the heart rate by 0.3 bpm for each 1 ng/ml. The kinetic analysis also demonstrated that the chronotropic effects of cocaine decline more rapidly than either plasma levels or biophase concentrations. This progressive attenuation in intensity of the chronotropic effect of a given biophase cocaine concentration could be modeled as a first-order process and is compatible with either the intervention of homeostatic reflex mechanisms or the phenomenon of acute tolerance. |
| Databáze: | OpenAIRE |
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