Oral single doses of erythromycin and roxithromycin may increase the effects of midazolam on human performance
| Autor: | J. Vanakoski, M. Törnwall, Mauri J. Mattila, J. J. Idänpään-Heikkilä |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Adult
Male Triazolam genetic structures medicine.drug_class Health Toxicology and Mutagenesis Sedation Midazolam Erythromycin Administration Oral Capsules Pharmacology Toxicology 030226 pharmacology & pharmacy Hypnotic 03 medical and health sciences 0302 clinical medicine Double-Blind Method Oral administration mental disorders Medicine Humans heterocyclic compounds Antibacterial agent Roxithromycin business.industry Brain Drug Synergism 030206 dentistry 3. Good health Drug Combinations surgical procedures operative Anesthesia Female medicine.symptom business psychological phenomena and processes Psychomotor Performance medicine.drug |
| Zdroj: | Pharmacologytoxicology. 73(3) |
| ISSN: | 0901-9928 |
| Popis: | Macrolide antibiotics are known to inhibit the metabolism of triazolam and midazolam in vitro and in vivo. To find out if significant interactions take place after single oral doses of these agents to man, 0.25 mg triazolam and 5, 10 and 15 mg of midazolam in capsule form were given with and without 750 mg erythromycin or 300 mg roxithromycin to parallel groups of healthy subjects in four placebo-controlled double-blind studies. Objective tests and subjective assessments were made before the intake of hypnotics and 30 and 90 min after it. In Study I, triazolam impaired letter cancellation, the combination triazolam + erythromycin impaired digit symbol substitution and letter cancellation, and triazolam + roxithromycin impaired digit symbol substitution, all at 90 min. In Study II, midazolam 5 mg and midazolam 10 mg proved quite inert but the combination midazolam 5 mg + erythromycin impaired digit symbol substitution. In Study III, both midazolam 10 mg and midazolam 15 mg impaired digit substitution and letter cancellation, the effects of 15 mg being more prominent. The strongest drug effects were found with midazolam 10 mg + erythromycin which differed from placebo and midazolam (10 mg and 15 mg) in several objective and subjective test variables. In Study IV, the combination midazolam 10 mg + roxithromycin impaired several objective and subjective variables but it was not stronger than midazolam 15 mg. These results were supported by the direct measurements of plasma midazolam in three subjects: erythromycin increased plasma midazolam more than roxithromycin and enhanced midazolam effects following the intake of midazolam 10 mg. Our results suggest that sedation produced by hypnotic doses of midazolam is enhanced by erythromycin and perhaps by roxithromycin after single oral doses. The combined effects of triazolam together with erythromycin and roxithromycin were unclear, partly due to the relatively lower dose of triazolam. |
| Databáze: | OpenAIRE |
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