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
Finasteride
63 ± 21 <1 90 2.3 ± 0.8 1.1 ± 0.2 7.9 ± 2.5 1-2 a 37 (27-49) ng/mL a
i RD, Aged
i RD, Aged
a
Following a single 5-mg oral dose given to healthy adults. Drug accumulates 2-fold with
once-daily dosing.
Flecainide a
70 ± 11 43 ± 3 61 ± 10 5.6 ± 1.3 b 4.9 ± 0.4 c 11 ± 3 b ~3 (l-6) d 458 ± 100 ng/mL d
b MI b RD, LD, CHF a Cirr a RD, LD, CHF
a Child
b Child
a
Racemic mixture; enantiomers exert similar electrophysiological effects. b Metabolized by
CYP2D6 (polymorphic); except for a shortened elimination t 1/2
and nonlinear kinetics in extensive
metabolizers, CYP2D6 phenotype had no significant influence on flecainide pharmacokinetics
or pharmacodynamics. c V area
reported. d Following a 100-mg oral dose given twice daily
for 5 days in healthy adults. Similar levels for CYP2D6 extensive and poor metabolizers.
Fluconazole
>90 75 ± 9 11 ± 1 0.27 ± 0.07 0.60 ± 0.11 32 ± 5 1.7-4.3 a 10.6 ± 0.4 μg/mL a
i AIDS, Neo i RD a LD, RD, Prem
b RD, Prem a Prem, Neo b Child
a
Following a 200-mg oral dose given twice a day for 4 days to healthy adults.
References: Debruyne D, et al. Clinical pharmacokinetics of fluconazole. Clin
Pharmacokinet, 1993, 24:10–27.
Fludarabine a
Reference: Sudduth SL, et al. Finasteride: The first 5α-reductase inhibitor. Pharmacotherapy,
1993, 13:309–325; discussion 325–329.
Reference: Funck-Brentano C, et al. Variable disposition kinetics and electrocardiographic
effects of flecainide during repeated dosing in humans: Contribution of genetic factors, dosedependent
clearance, and interaction with amiodarone. Clin Pharmacol Ther, 1994,
55:256–269.
Varhe A, et al. Effect of fluconazole dose on the extent of fluconazole-triazolam interaction.
Br J Clin Pharmacol, 1996, 42:465–470.
— 24 ± 3 — 3.7 ± 1.5 2.4 ± 0.6 10-30 — 0.57 μg/mL b
b RD
a
Data from adult male and female cancer patients following IV administration. Fludarabine is
rapidly dephosphorylated to 2-fluoro-arabinoside-A (F-ara-A), transported into cells, and
phosphorylated to the active triphosphate metabolite. Pharmacokinetics of F-ara-A are
reported. b Following a single 25-mg/m 2 IV dose of fludarabine (30-minute infusion); no
accumulation after five daily doses.
References: Hersh MR, et al. Pharmacokinetic study of fludarabine phosphate (NSC 312887).
Cancer Chemother Pharmacol, 1986, 17:277–280. PDR54, 2000, p. 764. Plunkett W, et al.
Fludarabine: Pharmacokinetics, mechanisms of action, and rationales for combination therapies.
Semin Oncol, 1993, 20:2–12.