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

Duloxetine a
42.8 (18.5-71.2) — >90 10.6 ± 2.4 7.0 ± 1.3 9.3 (6.4-12) 4.5 (2.5-6) e 32.9 ng/mL e
b Smk b b LD c a LD c
b RD d
i RD d
a
Cleared primarily by CYP1A2- and CYP2D6-dependent metabolism. b ~30% lower bioavailability
based on population pharmacokinetic analysis; no dose adjustment recommended. c A 5-fold
increase in oral AUC in patients with moderate liver impairment. d A 2-fold increase in oral AUC in
patients with end-stage RD receiving intermittent dialysis. e Following a single 60-mg oral dose.
References: Lobo ED, et al. In vitro and in vivo evaluations of cytochrome P450 1A2 interactions
with duloxetine. Clin Pharmacokinet, 2008, 47:191–202. Lobo ED, et al. Population
Dutasteride a
60 (40-94) — 99 — b — b 840 c 1 (1-3) d 38 ± 13 ng/mL d
a
Dutasteride is cleared primarily by CYP3A-dependent metabolism. b CL/F = 0.20-0.37
mL/min/kg, and V/F = 4.3-7.1 L/kg; calculated from steady-state (24 wk) serum concentrations.
c Terminal t 1/2
reported. d Following a 0.5-mg dose given once daily to steady state (24
weeks).
Efavirenz a
— b <1 99.5-99.75 3.1 ± 1.2 c — SD: 52-76 c 4.1 ± 1.7 e 4.0 ± 1.7 μg/mL e
a Food i Child d MD: 40-55 c
a
Data from patients with HIV infection. No significant gender differences. Metabolized primarily
by CYP2B6 and to a lesser extent by CYP2A6 and through N-glucuronidation. b Absolute
oral bioavailability is unknown. Oral AUC increased 50% with high-fat meal. c Single dose (SD)
data reported for CL/F and both SD and multiple dose (MD) data for t 1/2
. Efavirenz is a weak
Eletriptan a
~50 9 (7-12) c 85 5.6 (3.7-6.7) c 2.0 (1.4-2.4) c 4.1 (2.8-5.5) c MF: 0.75-1.5 e 57-115 ng/mL f
a Food b b LD d a LD e
a
Cleared primarily by CYP3A-dependent metabolism. b Systemic exposure increased 20-30%
with high-fat meal. c Data from 50-μg/kg IV dose reported; lack of dose proportionality for oral
AUC between 20- and 40- or 80-mg doses. d Study in patients with mild to moderate hepatic
impairment. e Following single 20- to 80-mg oral doses; MF: migraine-free period; M: during a
migraine attack. f Range of mean values from different studies following a single 30-mg oral dose.
pharmacokinetics of orally administered duloxetine in patients: Implications for dosing
recommendation. Clin Pharmacokinet, 2009, 48:189–197. Drugs@FDA. Cymbalta label
approved on 6/16/09. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/
label/2009/021427s030lbl.pdf. Accessed May 17, 2010.
References: Clark RV, et al. Marked suppression of dihydrotestosterone in men with benign
prostatic hyperplasia by dutasteride, a dual 5-alpha-reductase inhibitor. J Clin Endocrinol
Metab, 2004, 89:2179–2178. Keam SJ, et al. Dutasteride: A review of its use in the management
of prostate disorders. Drugs, 2008, 68:463–485.
inducer of CYP3A4 and its own metabolism. d 3-16 years of age, no difference in weightadjusted
CL/F compared to adult. e Following a 600-mg oral dose given daily to steady state.
References: Adkins JC, et al. Efavirenz. Drugs, 1998, 56:1055–1064. PDR54, 2000, p. 981.
Villani P, et al. Pharmacokinetics of efavirenz (EFV) alone and in combination therapy with
nelfinavir (NFV) in HIV-1 infected patients. Br J Clin Pharmacol, 1999, 48:712–715.
M: 2.0-2.8 e
References: McCormack PL, et al. Eletriptan: A review of its use in the acute treatment of
migraine. Drugs, 2006, 66:1129–1149. Milton KA, et al. Pharmacokinetics, pharmacodynamics,
and safety of the 5-HT(1B/1D) agonist eletriptan following intravenous and oral administration.
J Clin Pharmacol, 2002, 42:528–539. Drugs@FDA. Relpax label approved on
12/26/09. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21016_
relpax_lbl.pdf. Accessed May 17, 2010.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1925