Flurazepam pharmacokinetics

Benzodiazepines have similar pharmacological properties and are used in anxiety and insomnia. The choice of which benzodiazepine to use usually lies with the pharmacodynamic and pharmacokinetic properties, which vary across the class. For example, diazepam, flurazepam and nitrazepam have a prolonged duration of action whereas lorazepam and temazepam have a shorter duration of action. 

Hilbert JM, Battista D. Quazepam and flurazepam differential pharmacokinetic and pharmacodynamic characteristics. J Clin Psychiatry 1991 52(Suppl) 21-6. 

Example flurazepam hydrochloride Route PO Pregnancy Pharmacokinetic Absorbed ... 

The choice of a particular benzodiazepine is based on its pharmacokinetic profile. When used as a single dose, the extent of distribution and elimination half-life is important in predicting the duration of action. However, after multiple dosing, the elimination half-life and formation of active metabolites determine the extent of drug accumulation and resultant clinical effects." The benzodiazepine pharmacokinetic profiles are summarized in Table 71-4. The onset of action depends on the rate of absorption. Flurazepam and triazolam are absorbed rapidly. Temazepam is less lipophilic and has a slower onset of effect. Sedation after flurazepam, estazolam, and quazepam occurs within 1 to 2 hours after ingestion." Triazolam is redistributed quickly because of its high lipophilicity and thus has a short duration of effect." Estazolam and temazepam are intermediate in their duration of action. The therapeutic effects of flurazepam and quazepam are long in comparison because of the active metabolites. 

Rutledge, D.R. Abadi, A.H. Lopez, L.M. Liquid chromatographic determination of celiprolol, diltiazem, desmethyidiltiazem and deacetyldiltiazem in plasma using a short alkyl chain silanol deactivated column. J.Pharm.Biomed.Anal., 1994, 12, 135-140 [extracted metabolites, celiprolol LOD 3 ng/mL] Sigusch, H. Henschel, L. Kraul, H. Merkel, U. Hoffmann, A. Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects. Pharmazie, 1994, 49, 675-679 [pharmacokinetics SPE extracted metabolites flurazepam (IS)]... 

Table 19.1. Some Properties and Pharmacokinetics of the Benzodiazepine Sedatix Parameters Estazolam Flurazepam Quazepam Temazepam...

The pharmacokinetic profile for each of the benzodiazepines is shown in Table 19.1. The benzodiazepines that are slowly eliminated or are metabolized to slowly eliminated active metabolites can be used as hypnotics. For example, flurazepam is primarily metabolized by ... 

Flurazepam is administered orally as the dihydrochloride salt. It is rapidly N-dealkylated to give the 2 -fluoro derivative of N-desmethyIdiazepam, and it subsequently follows the same metabolic pathways as chlordiazepoxide and diazepam (Fig. 22.18). The half-life of flurazepam is fairly long ( 7 hours) consequently, it has the same potential as chlordiazepoxide and diazepam to produce cumulative clinical effects and side effects (e.g., excessive sedation) and residual pharmacological activity, even after discontinuation. Chlorazepate is yet another benzodiazepine that is rapidly metabolized (3-decarboxylation) to N-desmethyIdiazepam and so shares similar clinical and pharmacokinetic properties to chlordiazepoxide and diazepam. 

---