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

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APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
Table AII–1
Pharmacokinetic Data (Continued)
BIOAVAILABILITY URINARY BOUND IN CLEARANCE VOL. DIST. HALF-LIFE PEAK TIME PEAK
(ORAL) (%) EXCRETION (%) PLASMA (%) (mL/min/kg) (L/kg) (hours) (hours) CONCENTRATION
Ibuprofen a
>80 <1 >99 b 0.75 ± 0.20 b,c 0.15 ± 0.02 c 2 ± 0.5 b 1.6 ± 0.3 d 61.1 ± 5.5 μg/mL d
i RA, Alb a CF a CF i RA, CF, Child
i Child, RA
a LD
a
Racemic mixture. Kinetic parameters for the active S-(+)-enantiomer do not differ from those
for the inactive R-(–)-enantiomer when administered separately; 63 ± 6% of the R-(–)-
enantiomer undergoes inversion to the active isomer. b Unbound percent of S-(+)-ibuprofen
(0.77 ± 0.20%) is significantly greater than that of R-(–)-ibuprofen (0.45 ± 0.06%). Binding of
each enantiomer is concentration dependent and is influenced by the presence of the optical
Idarubicin a
I: 28 ± 4 <5 1: 97 29 ± 10 24.7 ± 5.9 I: 15.2 ± 3.7 I: 5.4 ± 2.4 c I: 6.9 ± 0.1 ng/mL c
IL: 94 b RD b IL: 41 ± 10 IL: 7.9 ± 2.3 c IL: 22 ± 4 ng/mL c
a
Data from male and female patients with cancer. Idarubicin (I) undergoes rapid metabolism
to a major active (equipotent) metabolite, idarubicinol (IL). b Mild to moderate renal impairment.
c Following a single 30- to 35-mg/m 2 oral dose.
Imatinib a
antipode, leading to nonlinear elimination kinetics. c CL/F and V ss
/F reported. d Following a
single 800-mg dose of racemate. A level of 10 μg/mL provides antipyresis in febrile children.
References: Lee EJ, et al. Stereoselective disposition of ibuprofen enantiomers in man. Br J
Clin Pharmacol, 1985, 19:669–674. Lockwood GF, et al. Pharmacokinetics of ibuprofen in
man. I. Free and total area/dose relationships. Clin Pharmacol Ther, 1983, 34:97–103.
IL: a RD b
References: Camaggi CM, et al. Idarubicin metabolism and pharmacokinetics after intravenous
and oral administration in cancer patients: A crossover study. Cancer Chemother
Pharmacol, 1992, 30:307–316. Robert J. Clinical pharmacokinetics of idarubicin. Clin
Pharmacokinet, 1993, 24:275–288. Tamassia V, et al. Pharmacokinetic study of intravenous
and oral idarubicin in cancer patients. Int J Clin Pharmacol Res, 1987, 7:419–426.
98 (87-111) 5 95 3.3 ± 1.2 6.2 ± 2.2 22 ± 4 3.3 ± 1.1 b 2.6 ± 0.8 μg/mL b
a
Imatinib is metabolized primarily by CYP3A4. b Following a 400-mg oral dose given once
daily to steady state.
References: Peng B, et al. Absolute bioavailability of imatinib (Glivec) orally versus intravenous
infusion. J Clin Pharmacol, 2004, 44:158–162. Peng B, et al. Pharmacokinetics and
pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients.
J Clin Oncol, 2004, 22:935–942. Product information: Gleevec TM (imatinib mesylate). Basel,
Switzerland, Novartis, 2004.