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

Hydroxychloroquine a
79 ± 12 27 45 ± 3 11.9 ± 5.4 b 525 ± 158 1056 (624-1512) 3.2 (2-4.5) 46 ng/mL (34-
79 ng/mL) c
a
Hydroxychloroquine is marketed as a racemic mixture of R- and S-hydroxychloroquine. Data for
the racemic mixture is reported. b Plasma clearance is reported. Hydroxychloroquine accumulates
in red blood cells with an average blood-to-plasma ratio of 7.2. Blood clearance of hydroxychloroquine
is 1.3 mL/min/kg. c Following oral administration of a single 155-mg tablet.
Hydroxyurea a
108 ± 18 35.8 ± 14.2 Negligible 72 ± 17 mL/ 19.7 ± 4.6 L/m 2 3.4 ± 0.7 IV: 0.5 c IV: 1007 ± 371 μM c
min/m 2b
(79-108) (36.2-72.3) (2.8-4.5) PO: 1.2 ± 1.2 c PO: 794 ± 241 μM c
a
Data from male and female patients treated for solid tumors. A range of mean values from
multiple studies is shown in parentheses. b Nonrenal elimination of hydroxyurea is thought to
exhibit saturable kinetics through a 10- to 80-mg/kg dose range. c Following a single 2-g,
30-minute IV infusion or oral dose.
Hydroxyzine a
— — — A: 9.8 ± 3.3 b A: 16 ± 3 b A: 20 ± 4 b A: 2.1 ± 0.4 d A: 72 ± 11 ng/mL d
C: 32 ± 11 b C: 19 ± 9 b C: 7.1 ± 2.3 b,c C: 2.0 ± 0.9 d C: 47 ± 17 ng/mL d
a Aged
a Aged, LD
a
Hydroxyzine is metabolized to an active metabolite, cetirizine. Plasma concentrations of cetirizine
exceed those of the parent drug; its t 1/2
is similar to that of hydroxyzine when formed
from parent drug. Hydroxyzine data for adults (A) and children (C) are reported. b CL/F, V d
/F,
and t 1/2
after oral dose reported. c t 1/2
increases with increasing age (1-15 years of age).
d
Following a single 0.7-mg/kg oral dose given to healthy adults and children.
References: Paton DM, et al. Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines).
Clin Pharmacokinet, 1985, 10:477–497. Simons FE, et al. Pharmacokinetics and
Ibandronate a
References: Tett SE, et al. A dose-ranging study of the pharmacokinetics of hydroxychloroquine following
intravenous administration to healthy volunteers. Br J Clin Pharmacol, 1988, 26:303–313.
Tett SE, et al. Bioavailability of hydroxychloroquine tablets in healthy volunteers. Br J Clin
Pharmacol, 1989, 27:771–779.
References: Gwilt PR, et al. Pharmacokinetics and pharmacodynamics of hydroxyurea. Clin
Pharmacokinet, 1998, 34:347–358. Rodriguez GI, et al. A bioavailability and pharmacokinetic
study of oral and intravenous hydroxyurea. Blood, 1998, 91:1533–1541.
antipruritic effects of hydroxyzine in children with atopic dermatitis. J Pediatr, 1984,
104:123–127. Simons FE, et al. The pharmacokinetics and antihistaminic of the HI receptor
antagonist hydroxyzine. J Allergy Clin Immunol, 1984, 73(pt 1):69–75. Simons FE, et al. The
pharmacokinetics and pharmacodynamics of hydroxyzine in patients with primary biliary cirrhosis.
J Clin Pharmacol, 1989, 29:809–815. Simons KJ, et al. Pharmacokinetic and pharmacodynamic
studies of the H 1
-receptor antagonist hydroxyzine in the elderly. Clin Pharmacol Ther,
1989, 45: 9–14.
0.63 54 ± 13 85 1.8 ± 0.1 5.8 ± 1.5 37 ± 5 1 11 ± 4 ng/mL c
b RD b
a
Cleared primarily by the kidney. b Exposure increases 50-100% in patients with moderate and
severe renal impairment. c Following a single 50-mg oral dose.
References: Barrett J, et al. Ibandronate: A clinical pharmacological and pharmacokinetic update.
J Clin Pharmacol, 2004, 44:951–965. Bergner R, et al. Renal safety and pharmacokinetics of
ibandronate in multiple myeloma patients with or without impaired renal function. J Clin
Pharmacol, 2007, 47:942–950.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
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