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

Ambrisentan a
— b — 99 — c — 9 d 2-3 e 1200 ng/mL e
i RD
a
Ambrisentan appears to be cleared primarily by the liver; however, the relative contribution from
metabolism (glucuronidation and oxidation) versus biliary excretion is unclear. It is exported into
the canalicular space of sandwich-cultured hepatocytes, possibly by P-glycoprotein. There also is
evidence to suggest that it undergoes active hepatic uptake by organic anion transporting polypeptide
(OATP) transporters. b The absolute bioavailability is unknown. c No IV dose data available; CL/F =
0.27 mL/min/kg following an oral dose in patients with pulmonary arterial hypertension (PAH).
Amikacin
— 98 4 ± 8 a 1.3 ± 0.6 0.27 ± 0.06 2.3 ± 0.4 — 26 ± 4 μg/mL b
CL = 0.6CL cr
+ 0.14 i Aged, Child, CF a RD
b Obes b Obes i Obes
a CP a Neo b Burn, Child, CF
a
At a serum concentration of 15 μg/mL. b Following a 1-hour IV infusion of a 6.3 ± 1.4-mg/kg
dose given three times a day to steady state in patients without renal impairment.
Amiodarone a
46 ± 22 0 99.98 ± 0.01 1.9 ± 0.4 b 66 ± 44 25 ± 12 days c 2-10 d 1.5-2.4 μg/mL d
i Aged, Fem,
i Aged, Fem, RD
CHF, RD
a
Significant plasma concentrations of an active desethyl metabolite are observed (ratio of
drug/metabolite ~l); t 1/2
for metabolite = 61 days. b Metabolized by CYP3A. c Longer t 1/2
noted
in patients (53 ± 24 days); all reported t 1/2
s may be underestimated because of insufficient
length of sampling. d Following a 400-mg/day oral dose to steady state in adult patients.
Amlodipine a
d
Effective t 1/2
for accumulation of drug with multiple dosing in patients with PAH. A longer
terminal t 1/2
= 14 hours also reported. e Following a 10-mg oral dose, given once a day to
steady state in patients with PAH.
References: Croxtall JD, et al. Ambrisentan. Drugs, 2008, 68:2195–2204. Drugs@FDA.
Letairis NDA and label. NDA approved on 5/15/07; label approved on 8/5/09. Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022081s010lbl.pdf.
Reference: Bauer LA, et al. Influence of age on amikacin pharmacokinetics in patients without
renal disease. Comparison with gentamicin and tobramycin. Eur J Clin Pharmacol, 1983,
24:639–642.
74 ± 17 10 93 ± 1 5.9 ± 1.5 16 ± 4 39 ± 8 5.4-8.0 b 18.1 ± 7.1 ng/mL b
i Aged i Aged i RD i Aged i RD a Aged
b Aged, Hep
a Aged, Hep
a
Racemic mixture; in young, healthy subjects, there are no apparent differences between the
kinetics of the more active R-enantiomer and S-enantiomer. b Following a 10-mg oral dose
given once daily for 14 days to healthy male adults.
Reference: Gill J, et al. Amiodarone. An overview of its pharmacological properties, and
review of its therapeutic use in cardiac arrhythmias. Drugs, 1992, 43:69–110.
Reference: Meredith PA, et al. Clinical pharmacokinetics of amlodipine. Clin Pharmacokinet,
1992, 22:22–31.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1903