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

Aripiprazole a
87 <1 >99 0.83 ± 0.17 b 4.9 b 47 ± 10 3.0 ± 0.6 c 242 ± 36 ng/mL c
a
Eliminated primarily by CYP2D6- and CYP3A4-dependent metabolism. The major metabolite,
dehydro-aripiprazole, has affinity for D 2
receptors similar to parent drug; found at 40% of
parent drug concentration in plasma; t 1/2
is 94 hours. CYP2D6 poor metabolizers exhibit
increased exposure (80%) to parent drug but reduced exposure (30%) to the active metabolite.
No significant gender differences. b CL/F and V/F at steady state reported. c Following a 15-mg
oral dose given once daily for 14 days.
Atazanavir a
— b 7 86 3.4 ± 1.0 c 1.6-2.7 c 7.9 ± 2.9 2.5 d 5.4 ± 1.4 μg/mL d
a Food b LD a LD
a
Undergoes extensive hepatic metabolism, primarily by CYP3A. Pharmacokinetic data
reported for healthy adults. No significant gender or age differences. b Absolute bioavailability
is not known, but food enhances the extent of absorption. c CL/F and V/F reported. Metabolic
elimination affected by inhibitors and inducers of CYP3A. Co-administration with low-dose
Atenolol a
58 ± 16 94 ± 8 <5 2.4 ± 0.3 1.3 ± 0.5 b 6.1 ± 2.0 c 3.3 ± 1.3 d 0.28 ± 0.09 μg/mL d
b Aged
a RD, Aged
a
Atenolol is administered as a racemic mixture. No significant differences in the pharmacokinetics
of the enantiomers. b V area
reported. c t 1/2
of R- and S-atenolol are similar. d Following a
single 50-mg oral dose.
Atomoxetine a
References: DeLeon A, et al. Aripiprazole: A comprehensive review of its pharmacology,
clinical efficacy, and tolerability. Clin Ther, 2004, 26:649–666. Mallikaarjun S, et al.
Pharmacokinetics, tolerability, and safety of aripiprazole following multiple oral dosing in
normal healthy volunteers. J Clin Pharmacol, 2004, 44:179–187. PDR58, 2004,
pp. 1034–1035.
ritonavir increases systemic atazanavir exposure. d Following a 400-mg oral dose given with a
light meal once daily to steady state.
References: Orrick JJ, et al. Atazanavir. Ann Pharmacother, 2004, 38:1664–1674. PDR58,
2004, p. 1081.
EM: 63 b 1-2% 98.7 ± 0.3 EM: 6.2 b EM: 2.3 b EM: 5.3 b EM/PM: 2 c EM: 160 ng/mL c
PM: 94 b PM: 0.60 b PM: 1.1 b PM: 20 b PM: 915 ng/mL c
EM: b LD
a
Metabolized by CYP2D6 (polymorphic). Poor metabolizers (PM) exhibit a higher oral
bioavailability, higher C max
, lower CL, and longer t 1/2
than extensive metabolizers (EM). No
differences between adults and children >6 years of age. b CL/F, V/F, and t 1/2
measured at
steady state. c Following a 20-mg oral dose given twice daily for 5 days.
References: Boyd RA, et al. The pharmacokinetics of the enantiomers of atenolol. Clin
Pharmacol Ther, 1989, 45:403–410. Mason WD, et al. Kinetics and absolute bioavailability of
atenolol. Clin Pharmacol Ther, 1979, 25:408–415.
References: Sauer JM, et al. Disposition and metabolic fate of atomoxetine hydrochloride:
The role of CYP2D6 in human disposition and metabolism. Drug Metab Dispos, 2003,
37:98–107. Simpson D, et al. Atomoxetine: A review of its use in adults with attention deficit
hyperactivity disorder. Drugs, 2004, 64:205–222.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
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