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

Esomeprazole a
Es: 89 (81-98) b Es/Rac: <1 Es/Rac: 95-97 Es: 4.1 (3.3-5.0) c,d Es: 0.25 Es: 0.9 (0.7-1.0) d Es: 1.5 Es: 4.5 (3.8-5.7) μM f
(0.23-0.27) Rac: 0.7 ± 0.5 (1.3-1.7) f Rac, EM: 0.68 ±
Rac: 53 ± 29 b Rac: 7.5 ± 2.7 c Rac: 0.34 ± 0.09 a LD e Rac, EM: ~1 g 0.43 μM g
b LD e Rac, PM: ~3-4 g Rac, PM: 3.5 ±
1.4 μM g
a
Esomeprazole is the S-enantiomer of omeprazole. Both esomeprazole (Es) and racemic
omeprazole (Rac) are available. Data for both formulations are reported. b Bioavailability
determined after multiple dosing. Lower Es values 64% (54-75%) reported for single dose.
c
The metabolic CL of the Es is slower than that of the R-enantiomer. Both Es and Rac are
metabolized by CYP2C19 (polymorphic) and CYP3A4. CL of Es and Rac is decreased and
t 1/2
increased in CYP2C19 poor metabolizers. d Following a single 40-mg IV dose. CL of Es
decreases and t 1/2
of Es increases with multiple dosing. e Reduced CL and increased t 1/2
in
patients with severe (Childs-Pugh class C) hepatic impairment. f Following a 40-mg oral dose
Eszopiclone, a Zopiclone
— Es: <10 Es: 52-59 — b — c Es: 7.2 ± 1.3 Es: 1 (0.4-2.1) Es: 39.8 ± 8.6 ng/mL f
a
Eszopiclone is the (S)-isomer of zopiclone. Pharmacokinetic data after dosing of eszopiclone
(Es) is shown. Es is metabolized extensively by CYP3A4 and CYP2E1. b CL/F following a
15-mg oral dose of zopiclone is 2.7 mL/min/kg for Es and 4.4 mL/min/kg for racemic zopiclone.
c V/F following a 15-mg oral dose of racemic zopiclone is 1.4 L/ kg for eszopiclone and
2 L/kg for racemic zopiclone. d Study in mild, moderate, and severe RD. e In patients with
severe hepatic impairment. f Following 3-mg Es given once daily to steady state.
Ethambutol
of Es given once daily for 5 days to healthy subjects of unspecified CYP2C19 phenotype.
g
Following a 20-mg oral dose of Rac given twice daily for 4 days to healthy subjects phenotyped
as CYP2C19 extensive metabolizers (EM) and poor metabolizers (PM).
References: Andersson T, et al. Pharmacokinetic studies with esomeprazole, the (S)-isomer of
omeprazole. Clin Pharmacokinet, 2001, 40:411–426. Chang M, et al. Interphenotype differences
in disposition and effect on gastrin levels of omeprazole—Suitability of omeprazole as
a probe for CYP2C19. Br J Clin Pharmacol, 1995, 39:511–518.
Es: i RD d
Es: a LD e
77 ± 8 79 ± 3 6-30 8.6 ± 0.8 1.6 ± 0.2 3.1 ± 0.4 2-4 a 2-5 μg/mL a
a
Following a single 800-mg oral dose to healthy subjects. Concentrations >10 μg/mL can
adversely affect vision. No accumulation with once-a-day dosing in patients with normal
renal function.
References: Drugs@FDA. Lunesta label approved on 04/06/09. Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021476s012lbl.pdf. Accessed July
9, 2010. Najib J. Eszopiclone, a nonbenzodiazepine sedative-hypnotic agent for the treatment
of transient and chronic insomnia. Clin Ther, 2006, 28:491–516.
a RD
Reference: Holdiness MR. Clinical pharmacokinetics of the antituberculosis drugs. Clin
Pharmacokinet, 1984, 9:511–544.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
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