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
Allopurinol a
53 ± 13 12 — 9.9 ± 2.4 b 0.87 ± 0.13 A: 1.2 ± 0.3 A: 1.7 ± 1.0 c A: 1.4 ± 0.5 μg/mL c
a RD, Aged b O: 24 ± 4.5 O: 4.1 ± 1.4 c O: 6.4 ± 0.8 μg/mL c
a
Data from healthy male and female subjects. Allopurinol (A) is rapidly metabolized to the
pharmacologically active oxypurinol (O). b lncreased oxypurinol AUC during renal impairment
and in the elderly. c Following a single 300-mg oral dose.
Alosetron a
57 (33-97) b — 82 8.3 (6.5-10.8) 0.91 (0.70-1.12) 1.4 (1.3-1.6) 1 e 5.5 (4.8-6.4) ng/mL e
i RD c
b LD d
a
Alosetron is cleared primarily by CYP1A2-dependent hepatic metabolism. b Absolute
bioavailability of a 4-mg dose, as compared to IV infusion. c Study in patients with CL cr
= 4-56
mL/min. d Study in patients with moderate to severe liver impairment; oral AUC 1.6- to 14-fold
higher than control. e Following a 1-mg oral dose, given twice a day to steady state.
Alprazolam
References: PDR54, 2000, p. 1976. Tumheim K, et al. Pharmacokinetics and pharmacodynamics
of allopurinol in elderly and young subjects. Br J Clin Pharmacol, 1999, 48:501–509.
References: Balfour JA, et al. Alosetron. Drugs, 2000, 59:511–518. Drugs@FDA. Lotronex
NDA and label. NDA approved on 2/11/00; label approved on 4/1/08. Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P3.pdf
and http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021107s013lbl.pdf. Accessed
May 17, 2010. Koch KM, et al. Sex and age differences in the pharmacokinetics of alosetron.
Br J Clin Pharmacol, 2002, 53:238–242.
88 ± 16 20 71 ± 3 0.74 ± 0.14 a 0.72 ± 0.12 12 ± 2 1.5 (0.5-3.0) c 21 (15-32) ng/mL c
a LD b Obes, LD, i Obes, LD, a Obes, LD,
i Obes, Aged b Aged Aged b
Aged i RD i RD
a
Metabolically cleared by CYP3A and other cytochrome P450 isozymes. b Data from male
subjects only. c Mean (range) from 19 studies following a single 1-g oral dose given to adults.
Reference: Greenblatt DJ, et al. Clinical pharmacokinetics of alprazolam. Therapeutic implications.
Clin Pharmacokinet, 1993, 24:453–471.