A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Dalmane Pharmacology, Pharmacokinetics, Studies, Metabolism - Flurazepam
Dalmane Pharmacology, Pharmacokinetics, Studies, Metabolism - Flurazepam
CLINICAL PHARMACOLOGY
Flurazepam hydrochloride
is rapidly absorbed from the G.I. tract. Flurazepam is rapidly metabolized
and is excreted primarily in the urine. Following a single oral
dose, peak flurazepam plasma
concentrations occur at 30 to 60 minutes post-dosing. The mean
apparent half-life
of flurazepam is 2.3 hours. The blood
level profile of flurazepam
and its major metabolites was determined in man
following the oral administration
of 30 mg daily for 2 weeks.
The N1-hy-droxyethyl- flurazepam was measurable only during the
early hours after a 30 mg
dose and was not detectable
after 24 hours. The major metabolite
in blood was N1-desalkyl-flurazepam,
which reached steady-state (plateau) levels after 7 to 10 days of
dosing, at levels approximately five to sixfold greater than the
24-hour levels observed on Day 1. The half life
of elimination of
N1-des-alkyl- flurazepam ranged from 47 to 100 hours. The major
urinary metabolite
is conjugated N1-hydroxyethyl- flurazepam which accounts for 22
to 55 percent of the
dose. Less than 1% of the dose
is excreted in the urine
as N1-desalkyl-flurazepam.
The pharmacokinetic profile
may be responsible for the clinical
observation that flurazepam is increasingly effective on the second
or third night of consecutive use and that for one or two nights
after the drug is discontinued
both sleep latency
and total wake time may
still be decreased.
Geriatric Pharmacokinetics: The single dose pharmacokinetics of flurazepam were studied in 12 healthy geriatric subjects (aged 61 to 85 years). The mean elimination half-life of desalkyl-flurazepam was longer in elderly male subjects (160 hours) compared with younger male subjects (74 hours), while mean elimination half-life was similar in geriatric female subjects (120 hours) and younger female subjects (90 hours). After multiple dosing, mean steady-state plasma levels of desalkyl-flurazepam were higher in elderly male subjects (81 ng/mL) compared with younger male subjects (53 ng/mL), while values were similar between elderly female subjects (85 ng/mL) and younger female subjects (86 ng/mL). The mean washout half-life of desalkyl-flurazepam was longer in elderly male and female subjects (126 and 158 hours, respectively) compared with younger male and female subjects (111 and 113 hours, respectively). 1
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