Title |
Pharmacokinetics of flutoprazepam, a novel benzodiazepine drug, in normal subjects
|
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Published in |
European Journal of Drug Metabolism and Pharmacokinetics, October 1989
|
DOI | 10.1007/bf03190114 |
Pubmed ID | |
Authors |
N. Barzaghi, L. Leone, M. Monteleone, G. Tomasini, E. Perucca |
Abstract |
The single dose pharmacokinetics of flutoprazepam and its active N-desalkyl metabolite were determined in 8 normal subjects by using newly developed, highly sensitive, GC-MS and HPLC techniques. Following a 2 mg dose of the drug, the concentrations of unchanged flutoprazepam in serum were extremely low (below 5 ng/ml at 2 h) and declined rapidly to undetectable levels within 6-9 h after dosing. At all sampling times, the serum concentration of the N-dealkylated metabolite (N-desalkylflurazepam) was much greater than that of the parent compound. This metabolite appeared in serum rapidly (within 2 h), reached a peak between 2 and 12 h and declined slowly, with an elimination half-life of about 90 h on average. The serum concentration of two additional putative metabolites (3-hydroxy-flutoprazepam and N-desalkyl-3-hydroxy-flutoprazepam) was below the limit of detection (2 ng/ml) in all samples. Mild CNS effects (documented by prolonged choice reaction time) were present at 2 and 4 h but were no longer detectable at 9 h. It is suggested that unchanged flutoprazepam is unlikely to contribute significantly to clinical effects and that the drug exerts its therapeutic activity through conversion to the slowly eliminated N-desalkyl metabolite. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 8 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Lecturer > Senior Lecturer | 1 | 13% |
Other | 1 | 13% |
Student > Doctoral Student | 1 | 13% |
Student > Bachelor | 1 | 13% |
Student > Ph. D. Student | 1 | 13% |
Other | 1 | 13% |
Unknown | 2 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 2 | 25% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 13% |
Chemistry | 1 | 13% |
Biochemistry, Genetics and Molecular Biology | 1 | 13% |
Unknown | 3 | 38% |