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

Rivastigmine a
72 (22-119) b Negligible 40 13 ± 4 c 1.5 ± 0.6 c 1.4 ± 0.4 c,d 1.2 ± 1.0 e 26 ± 10 ng/mL e
a Food, Dose b Food b Food
a
Rivastigmine is metabolized by cholinesterase. No apparent gender differences. b Following a
6-mg oral dose. Bioavailability increases with dose; following a 3-mg dose, the median
bioavailability is 36%. c IV dose of 2 mg. d The pharmacodynamic t 1/2
is ~10 hours due to tight
binding to acetylcholinesterase. e Following oral administration of a 6-mg capsule. C max
increases more than proportionally at doses >3 mg.
Rizatriptan a
47 F: 28 ± 9 b 14 F: 12.3 ± 1.4 b F: 1.5 ± 0.2 F: 2.2 SD: 0.9 ± 0.4 e SD: 20 ± 4.9 ng/mL e
M: 29 b M: 18.9 ± 2.8 b M: 2.2 ± 0.4 M: 2.4 MD: 4.8 ± 0.7 e MD: 37 ± 13 ng/mL e
b LD, c RD d
a
Data from healthy adult male (M) and female (F) subjects. Oxidative deamination catalyzed
by MAO-A is the primary route of elimination. N-desmethyl rizatriptan (DMR) is a minor
metabolite (~14%) that is active and accumulates in blood. b Evidence of minor dosedependent
metabolic CL and urinary excretion. c CL/F reduced, moderate hepatic impairment.
d
CL/F reduced, severe renal impairment. e Following a 10-mg single (SD) and multiple (MD)
oral dose (10 mg every 2 hours × 3 doses × 4 days). DMR C max
is 8.5 and 26.2 ng/mL with
SD and MD, respectively.
Ropinirole a
55 <10 ~40 11.2 ± 5.0 b 7.5 ± 2.4 b 6 b 1.0 (0.5-6.0) d 7.4 (2.4-13) ng/mL d
b Aged c a Food b Food
i RD
a
Data from male and female patients with Parkinson’s disease. Metabolized primarily by
CYP1A2 to inactive N-deisopropyl and hydroxy metabolites. b CL/F, V d
/F, and t 1/2
reported for
oral dose. c CL/F reduced but dose titrated to desired effect. d Following a 2-mg oral dose given
three times daily to steady state.
Rosiglitazone a
References: Hossain M, et al. Estimation of the absolute bioavailability of rivastigmine in
patients with mild to moderate dementia of the Alzheimer’s type. Clin Pharmacokinet, 2002,
41:225–234. Williams BR, et al. A review of rivastigmine: A reversible cholinesterase
inhibitor. Clin Ther, 2003, 25:1634–1653.
References: Goldberg MR, et al. Rizatriptan, a novel 5-HT 1B/1D
agonist for migraine: Singleand
multiple-dose tolerability and pharmacokinetics in healthy subjects. J Clin Pharmacol,
2000, 40:74–83. Lee Y, et al. Pharmacokinetics and tolerability of intravenous rizatriptan in
healthy females. Biopharm Drug Dispos, 1998, 19:577–581. PDR54, 2000, p. 1912. Vyas KP,
et al. Disposition and pharmacokinetics of the antimigraine drug, rizatriptan, in humans. Drug
Metab Dispos, 2000, 28:89–95.
99 Negligible 99.8 0.68 ± 0.16 c 0.25 ± 0.08 c 3-4 c 1.0 d 598 ± 117 ng/mL d
(0.49) (0.21)
b LD b b LD d b LD
i RD
a
Data from male and female patients with NIDDM. No significant gender differences.
Metabolized primarily by CYP2C8. b Reduced CL/F and CL/F unbound
, moderate to severe liver
impairment. c CL/F, V d
/F, and t 1/2
reported for oral dose. Shown in parentheses are mean values
from a population pharmacokinetic analysis. d Following a single 8-mg oral dose.
References: Bloomer JC, et al. In vitro identification of the P450 enzymes responsible for the
metabolism of ropinirole. Drug Metab Dispos, 1997, 25:840–844. PDR54, 2000, p. 3037.
Taylor AC, et al. Lack of a pharmacokinetic interaction at steady state between ropinirole and
L-dopa in patients with Parkinson’s disease. Pharmacotherapy, 1999, 79:150–156.
References: Baldwin SJ, et al. Characterization of the cytochrome P450 enzymes involved in the
in vitro metabolism of rosiglitazone. Br J Clin Pharmacol, 1999, 48:424–432. Patel BR, et al.
Population pharmacokinetics of rosiglitazone (R) in phase III clinical trials. Clin Pharmacol
Ther, 2000, 67:123. PDR54, 2000, p. 2981. Thompson K, et al. Pharmacokinetics of rosiglitazone
are unaltered in hemodialysis patients [abstract]. Clin Pharmacol Ther, 1999, 65:186.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1975