Inter- and intraindividual variability in the concentration-effect (sedation) relationship of flunitrazepam
| Autor: | P Wennerlund, S. Å. Eckernäs, B. Dahlström, A. Grahnén |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Male
medicine.drug_class Sedation Individuality Flunitrazepam Gas Chromatography-Mass Spectrometry Hypnotic Random Allocation Pharmacokinetics Humans Hypnotics and Sedatives Medicine Pharmacology (medical) Volunteer Pharmacology Dose-Response Relationship Drug business.industry Dose–response relationship Anesthesia Sedative Female medicine.symptom business Research Article medicine.drug Blood sampling |
| Zdroj: | British Journal of Clinical Pharmacology. 31:89-92 |
| ISSN: | 0306-5251 |
| DOI: | 10.1111/j.1365-2125.1991.tb03862.x |
| Popis: | 1. The relationship between plasma flunitrazepam concentrations and the degree of sedation was evaluated in 20 healthy subjects receiving two single oral doses of 1 mg flunitrazepam on two different occasions (1 week apart). The degree of sedation was rated blindly during the two treatment sessions in parallel with blood sampling (48 h). 2. A strong correlation between the concentrations of flunitrazepam in plasma and the degree of sedation was found according to the sigmoid Emax model. The plasma drug concentration producing 50% of maximal effect (EC50) was found to be 7.0 and 6.5 ng ml-1 on the two occasions, respectively. The variability in EC50 between subjects was larger (C.V. 39%) than the variability within subjects (C.V. 27%). 3. The steepness of the concentration-response curve as reflected in the slope factor(s) showed a virtual 'all or none' response to flunitrazepam with s values ranging from 3 to 30 with a mean of about 14. 4. The results in young healthy subjects suggest that the present dosage recommendations for temporary insomnia (1-2 mg) may be inappropriate; the dose can probably be reduced to 0.5 mg in some patients to achieve moderate sedation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text