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Pharmacokinetics of flunitrazepam following single dose oral administration in liver disease patients compared with healthy volunteers
Author(s) -
DrouetCoassolo C.,
Iliadis A.,
Coassolo P.,
Antoni M.,
Cano JP
Publication year - 1990
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1990.tb00044.x
Subject(s) - flunitrazepam , pharmacokinetics , cirrhosis , medicine , liver disease , metabolite , hepatitis , gastroenterology , free fraction , oral administration , desmethyl , hepatitis c , pharmacology , benzodiazepine , receptor
Summary— The pharmacokinetic behaviour of flunitrazepam and its main active metabolite, N ‐desmethyl flunitrazepam, was investigated in 12 patients with liver disease (cirrhosis or hepatitis) compared to 6 healthy volunteers. A gas‐liquid chromatographic method allowing for simultaneous determination of flunitrazepam and N ‐desmethyl flunitrazepam in plasma samples was developed. The accuracy and the precision near the quantification limit of ca. 1 ng/ml were better than 5%. Plasma levels of flunitrazepam were not significantly altered by hepatic failure, whereas plasma levels of N ‐desmethyl flunitrazepam were lower in patients than in heathly subjects. Pharmacokinetic parameters did not differ significantly between healthy subjects and liver disease patients: the oral clearance was 3.5 ± 0.8, 3.5 ± 1.9 and 4.0 ± 1.2 ml/min/kg, respectively in healthy subjects, patients with hepatitis and patients with cirrhosis. The apparent elimination half‐life was 22 ± 5 h in healthy subjects, 25 ± 10 h in patients with hepatitis and 20 ± 6 h in patients with cirrhosis. However, the expected increase of the drug free fraction during liver disease could decrease the therapeutic and toxic ranges of flunitrazepam in these patients.