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

Moxifloxacin a
86 ± 1 21.9 ± 3.6 39.4 ± 2.4 2.27 ± 0.24 2.05 ± 1.15 15.4 ± 1.2 2.0 (0.5-6.0) b 2.5 ± 1.3 μg/mL b
a
Data from healthy adult male subjects. Moxifloxacin is metabolized by ST and UGT.
b
Following a single oral 400-mg dose.
Mycophenolate a
MM: ~0 MPA: <1 MPA: 97.5 MM: 120-163 MPA: 3.6-4 c MM: <0.033 MPA: 1.1-2.2 d MPA: 8-19 μg/mL d
MPA: 94 b RD b MPA: 2.5 ± 0.4 c MPA: 16.6 ± 5.8
b RD b
i LD
a
Data from healthy adult male and female subjects and organ transplant patients. No significant
gender differences. Mycophenolate mofetil (MM) is rapidly converted to the active
mycophenolic acid (MPA) after IV and oral doses. Kinetic parameters refer to MM and MPA
after a dose of MM. MPA metabolized by UGT to MPA-glucuronide (MPAG). MPA undergoes
enterohepatic recycling; MPAG is excreted into bile and presumably is hydrolyzed by
gut flora and reabsorbed as MPA. b Accumulation of MPA and MPAG and increased unbound
MPA; severe renal impairment. c CL/F and V area
/F reported for MPA. d Range of mean MPA
Nabumetone a
35 ~ 50 ~ 99 b 0.37 ± 0.25 c 0.79 ± 0.38 c 23 ± 4 Y: 4-5 d Y: 22-52 μg/mL d
a
Data are for the active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA). The conversion
of nabumetone to the active metabolite 6-MNA is mediated predominantly by CYP1A2.
b
99.7-99.8% over concentration range following multiple 1-g doses; 99.2-99.4% following
multiple 200-mg doses. c CL/F and V ss
/F reported; calculated assuming a 70-kg body weight.
Following IV dosing of 6-MNA, CL is 0.04-0.07 mL/min/kg and V ss
averages 0.11 L/kg.
d
Range of mean values from different studies following a 1-g oral dose given once daily for
7-14 days to young healthy adults (Y) and elderly patients with arthritis (E).
Naltrexone a
Reference: Stass H, et al. Pharmacokinetics and elimination of moxifloxacin after oral and
intravenous administration in man. J Antimicrob Chemother, 1999, 43(suppl B):83–90.
C max
and T max
from different studies following a 1- to 1.75-g oral dose given twice daily to
steady state in renal transplant patients.
References: Bullingham R, et al. Effects of food and antacid on the pharmacokinetics of single
doses of mycophenolate mofetil in rheumatoid arthritis patients. Br J Clin Pharmacol, 1996,
47:513–516. Bullingham RE, et al. Clinical pharmacokinetics of mycophenolate mofetil. Clin
Pharmacokinet, 1998, 34:429–455. Kriesche HUM, et al. MPA protein binding in uremic plasma:
Prediction of free fraction. Clin Pharmacol Ther, 1999, 65:184. PDR54, 2000, pp. 2617–2618.
i Aged i Aged a RD
i Aged
E: 4-7 d E: 37-70 μg/mL d
20 ± 5 2 21 18.3 ± 1.4 16.1 ± 5.2 10.3 ± 3.3 c 1 d 15-64 ng/mL d
b LD b
i LD
a
Naltrexone has an active metabolite, 6β-naltrexol, that circulates at greater concentrations
than naltrexone and has a 10-fold higher AUC than naltrexone after oral administration of naltrexone.
b The oral AUC of naltrexone was significantly increased in patients with liver impairment,
whereas the AUC of 6β-naltrexol was not changed. c A t 1/2
of 2.7 hours after IV
administration also reported. d Following a single 100-mg oral dose.
References: Davies NM. Clinical pharmacokinetics of nabumetone. The dawn of selective
cyclo-oxygenase-2 inhibition? Clin Pharmacokinet, 1997, 33:404–416. Hyneck ML. An
overview of the clinical pharmacokinetics of nabumetone. J Rheumatol, 1992, 19(suppl
36):20–24. Turpeinen M, et al. A predominate role of CYP1A2 for the metabolism of
nabumetone to the active metabolite, 6-methoxy-2-naphtylacetic acid, in human liver microsomes.
Drug Metab Dispos, 2009, 37:1017–1024.
References: Bullingham RES, et al. Clinical pharmacokinetics of narcotic agonist-antagonist
drugs. Clin Pharmacokinet, 1983, 8:332–343. Bertolotti M, et al. Effect of liver cirrhosis on
the systemic availability of naltrexone in humans. J Hepatol, 1997, 27:505–511.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
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