Premium
Inter‐ and intraindividual variability in the concentration‐effect (sedation) relationship of flunitrazepam.
Author(s) -
Grahnen A,
Wennerlund P,
Dahlstrom B,
Eckernas SA
Publication year - 1991
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1991.tb03862.x
Subject(s) - flunitrazepam , sedation , sedative , anesthesia , plasma concentration , medicine , hypnotic , blood sampling , pharmacokinetics , pharmacology , benzodiazepine , receptor
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.