DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
Table AII–1
Pharmacokinetic Data (Continued)
BIOAVAILABILITY URINARY BOUND IN CLEARANCE VOL. DIST. HALF-LIFE PEAK TIME PEAK
(ORAL) (%) EXCRETION (%) PLASMA (%) (mL/min/kg) (L/kg) (hours) (hours) CONCENTRATION
Lenalidomide a
>80 b 84 c 35 ± 4 2.8 e 0.8 e 3.3 1 (0.5-2.0) 568 ± 221 ng/mL f
i RD d b RD d a RD d
a
Lenalidomide is administered as a racemic mixture. Data for the racemate is shown. b Based
on urine recovery of unchanged drug after oral administration. Lenalidomide is primarily
eliminated via urinary excretion. c Percentage of oral dose recovered unchanged in urine.
d
Study in patients with mild, moderate, severe, and end-stage renal impairment; exposure
Letrozole a
99.9 ± 16.3 3.9 ± 1.4 60 0.58 ± 0.21 1.87 ± 0.46 45 ± 16 1.0 c 115 nM c
b LD b
a
Data from healthy postmenopausal female subjects. Metabolized by CYP3A4 and CYP2A6.
b
CL/F reduced, severe hepatic impairment. c Following a single 2.5-mg oral dose (tablet).
Levetiracetam a
~100 66 <10 0.96 0.5-0.7 7 ± 1 0.5-1.0 e ~10 μg/mL e
b RD, b Aged, LD c
a RD, b Aged
a Child d
a
Data from healthy adults and patients with epilepsy. No significant gender differences. b CL/F
reduced, mild renal impairment (cleared by hemodialysis). c CL/F reduced, severe hepatic
impairment. d CL/F increased, 6-12 years of age. e Following a single 500-mg dose given to
healthy adults.
Levodopa a
increases 150% in moderate renal impairment and 375% in severe renal impairment. e CL/F
and V/F reported. f Following a single 25-mg oral dose.
Reference: Chen N, et al. Pharmacokinetics of lenalidomide in subjects with various degrees
of renal impairment and in subjects on hemodialysis. J Clin Pharmacol, 2007, 47:1466–1475.
References: Lamb HM, et al. Letrozole. A review of its use in postmenopausal women with
advanced breast cancer. Drugs, 1998, 56:1125–1140. Sioufi A, et al. Absolute bioavailability
of letrozole in healthy postmenopausal women. Biopharm Drug Dispos, 1997, 18:779–789.
Reference: Physicians’ Desk Reference, 55th ed. Montvale, NJ, Medical Economics Co.,
2001, pp. 3206–3207.
41 ± 16 <1 — 23 ± 4 1.7 ± 0.4 1.4 ± 0.4
a Aged b Aged b Aged i Aged
86 ± 19 b 9 ± l b 0.9 ± 0.2 b 1.5 ± 0.3 b Y: 1.4 ± 0.7 c Y: 1.7 ± 0.8 μg/mL c
i Aged b Aged b Aged i Aged E: 1.4 ± 0.7 c E: 1.9 ± 0.6 μg/mL c
a
Naturally occurring precursor to dopamine. b Values obtained with concomitant carbidopa
(inhibitor of dopa decarboxylase). c Following a single 125-mg oral dose of levodopa given
with carbidopa (100 mg 1 hour before and 50 mg 6 hours after levodopa) in young (Y) and
elderly (E) subjects.
Reference: Robertson DR, et al. The effect of age on the pharmacokinetics of levodopa administered
alone and in the presence of carbidopa. Br J Clin Pharmacol, 1989, 28:61–69.