Extensive and enantioselective presystemic metabolism of dl-threo-methylphenidate in humans
| Autor: | Kamal K. Midha, Declan Quinn, John W. Hubbard, E. D. Korchinski, Nuggehally R. Srinivas |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Adult
Male Administration Oral Biological Availability Pharmacology mental disorders Slow Release Formulation Humans Medicine Prospective Studies Child Prospective cohort study Biological Psychiatry Intravenous dose business.industry Methylphenidate Stereoisomerism Plasma levels Metabolism Enantioselective pharmacokinetics Bioavailability Attention Deficit Disorder with Hyperactivity Child Preschool Delayed-Action Preparations Injections Intravenous Female business human activities medicine.drug |
| Zdroj: | Progress in Neuro-Psychopharmacology and Biological Psychiatry. 15:213-220 |
| ISSN: | 0278-5846 |
| Popis: | 1. Two pilot studies were carried out to investigate the enantioselective pharmacokinetics of methylphenidate (MPH) in children with attention deficit-hyperactivity disorder (ADHD). A more definitive study, which included administration of an intravenous dose, was carried out in healthy young men. 2. Serial plasma samples were harvested from predose to 8 hours in the first pilot study, predose to 12 hours in the second pilot study and predose to 16 hours in the definitive study. Plasma levels of the separate isomers d-MPH and 1-MPH were determined by an enantioselective gas chromatographic method. 3. In the first pilot study, 6 boys with ADHD each received his regular dose of MPH (10mg n = 5, 5mg n = 1), which contained equal proportions of d-MPH and 1-MPH in an immediate release formulation (MPH-IR). No MPH was detectable in the predose plasma. Thereafter, plasma levels of the more active d-MPH were 4 to 10 fold higher than those of 1-MPH. Plasma levels of 1-MPH were so low that it was not possible to monitor them beyond 4 hours in some children. 4. In the second pilot study, 5 boys and 1 girl with ADHD each received their regular dose (20mg) of a slow release formulation (MPH-SR). No MPH was detectable in the predose plasma. Thereafter, plasma levels of the more active d-MPH were 5 to 10 fold higher than those of 1-MPH. It was possible to monitor plasma levels of 1-MPH over the full 12 hour period of study in 5 of the 6 children.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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