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

Cetirizine a
Rac: >70 b Rac: 70.9 ± 7.8 Rac: 89.2 ± 0.4 Rac: 0.74 ± 0.19 c Rac: 0.58 ± 0.16 c Rac: 9.42 ± 2.4 Rac: 0.9 ± 0.2 g Rac: 313 ± 45
ng/mL g
Levo: >68 b Levo: 68.1 ± 10.2 Levo: 92.0 ± 0.3 Levo: 0.62 ± 0.11 c Levo: 0.41 ± 0.10 Levo: 7.8 ± 1.6 Levo: 0.8 ± 0.5 g Levo: 270 ± 40
ng/mL g
Rac: b LD, d
Rac: a LD,
RD, e Aged
RD, Aged
Levo: b RD
Levo: a RD
Rac/Levo:
Rac/Levo:
a Child f
b Child
a
Data from healthy male and female subjects receiving cetirizine (Rac) or the active R-enantiomer,
levocetirizine (Levo). b Based on recovery of unchanged drug in urine. c CL/F, V d
/F
reported for oral dose. d CL/F reduced, hepatocellular and cholestatic liver diseases. e CL/F
reduced, moderate to severe renal impairment. f CL/F increased, ages 1-5 years. g Following a
single 10-mg oral dose of Rac or 5 mg of Levo.
References: Baltes E, et al. Absorption and disposition of levocetirizine, the eutomer of cetirizine,
administered alone or as cetirizine to healthy volunteers. Fundam Clin Pharmacol,
2001, 15:269–277. Benedetti MS, et al. Absorption, distribution, metabolism and excretion of
Chloroquine a
~80 52-58 b S: 66.6 ± 3.3 c 3.7-13 b 132-261 b 10-24 days b,d IM: 0.25 e IV: 837 ± 248 ng/mL
R: 42.7 ± 2.1 PO: 3.6 ± 2.0 e IM: 57-480 ng/mL
i RD
PO: 76 ± 14 ng/mL
a
Active metabolite, desethylchloroquine, accounts for 20 ± 3% of urinary excretion; t 1/2
= 15 ±
6 days. Racemic mixture; kinetic parameters for the two isomers are slightly different [e.g.,
mean residence time = 16.2 days and 11.3 days for the R-isomer and S-isomer, respectively].
b
Range of mean values from different studies (IV administration). c Concentrates in red blood
cells. Blood-to-plasma concentration ratio for racemate = 9. d A longer t 1/2
(41 ± 14 days) has
been reported with extended blood sampling. e Following a single 300-mg IV dose (24-minute
Chlorpheniramine a
[14C]levocetirizine, the R enantiomer of cetirizine, in healthy volunteers. Eur J Clin
Pharmacol, 2001, 57:571–582. Horsmans Y, et al. Single-dose pharmacokinetics of cetirizine
in patients with chronic liver disease. J Clin Pharmacol, 1993, 33:929–932. Matzke GR, et al.
Pharmacokinetics of cetirizine in the elderly and patients with renal insufficiency. Ann Allergy,
1987, 59:25–30. PDR54, 2000, p. 2404. Spicák V, et al. Pharmacokinetics and pharmacodynamics
of cetirizine in infants and toddlers. Clin Pharmacol Ther, 1997, 61:325–330. Strolin Benedetti M,
et al. Stereoselective renal tubular secretion of levocetirizine and dextrocetirizine, the two enantiomers
of the H1-antihistamine cetirizine. Fundam Clin Pharmacol, 2008, 22:19–23.
infusion) of chloroquine HCl or a single 300-mg IM or oral dose of chloroquine phosphate given to
healthy adults. Effective concentrations against Plasmodium vivax and Plasmodium falciparum are
15 ng/mL and 30 ng/mL, respectively. Diplopia and dizziness can occur >250 ng/mL.
References: Krishna S, et al. Pharmacokinetics of quinine, chloroquine and amodiaquine.
Clinical implications. Clin Pharmacokinet, 1996, 30:263–299. White NJ. Clinical pharmacokinetics
of antimalarial drugs. Clin Pharmacokinet, 1985, 10:187–215.
41 ± 16 0.3-26 b 70 ± 3 1.7 ± 0.1 3.2 ± 0.3 20 ± 5 IR: 2-3 c IR: 16-71 ng/mL c
a Child i Child b Child SR: 5.7-8.1 c SR: 17-76 ng/mL c
a
Administered as a racemic mixture; reported parameters are for racemic drug. Activity comes
predominantly from S-(+)-enantiomer, which has a 60% longer t 1/2
than the R-(–)-enantiomer.
b
Renal elimination increases with increased urine flow and lower pH. c Range of data from different
studies following a 4-mg oral immediate-release (IR) dose given every 4-6 hours to
steady state or following an 8-mg oral sustained-release (SR) dose given every 12 hours to
steady state, both in healthy adults.
Reference: Rumore MM. Clinical pharmacokinetics of chlorpheniramine. Drug Intell Clin
Pharm, 1984, 18:701–707.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
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