Metabolism of haloperidol to pyridinium species in patients receiving high doses intravenously: Is HPTP an intermediate?
| Autor: | Gilles L. Fraser, Kathryn M. Avent, Richard R. Riker, Susan Pond, Cornelis J. Van der Schyf, Etsuko Usuki |
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| Rok vydání: | 1997 |
| Předmět: |
Adult
Male Pyridinium Compounds Urine Pharmacology General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound In vivo Haloperidol medicine Humans General Pharmacology Toxicology and Pharmaceutics Aged Chemistry Neurotoxicity General Medicine Metabolism Middle Aged medicine.disease In vitro Injections Intravenous Microsome Female Pyridinium Antipsychotic Agents medicine.drug |
| Zdroj: | Life Sciences. 61:2383-2390 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/s0024-3205(97)00955-7 |
| Popis: | The metabolism of haloperidol (HP) to the potentially neurotoxic pyridinium species, HPP+ and RHPP+, has been demonstrated in humans. In vitro studies in microsomes harvested from various animal species indicate that the tetrahydropyridines, HPTP and RHPTP, could be intermediates in this pathway. However, this has not yet been demonstrated in vivo in humans. In this study, plasma and urine collected from eight critically ill patients treated with high doses of intravenous HP were analyzed for HPTP and RHPTP using HPLC with electrochemical detection. However, neither HPTP nor RHPTP were detected despite plasma concentrations of HP and RHP higher than any previously reported. HPP+ and RHPP+ were both present in the urine in high concentrations and accounted for 1.1 +/- 0.5% and 5.3 +/- 3.6%, respectively, of the administered dose of HP. The apparent elimination half-lives of HPP+ and RHPP+ were 67.3 +/- 11.0 hr and 63.3 +/- 11.6 hr, respectively. The absence of HPTP and RHPTP in plasma and urine suggests that in humans these tetrahydropyridines either are insignificant intermediates in the metabolism of HP in vivo or are present only transiently at their site of formation and are not released into the circulation. |
| Databáze: | OpenAIRE |
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