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
Quinidine a
Sulfate: 80 ± 15 18 ± 5 87 ± 3 4.7 ± 1.8 b 2.7 ± 1.2 6.2 ± 1.8 IR: 1-3 c IV: 2.9 ± 1.0 μg/mL c
Gluconate: i CHF b LD, Hep, b CHF, Aged b CHF a Aged, LD ER: 6.3 ± 3.2 c IR: ~1.3 μg/mL c
71 ± 17 Neo, Preg i LD, Smk
i RD, CRI, a LD i CHF, RD ER: 0.53 ±
HL, Aged
0.22 μg/mL c
i Aged
a
Active metabolite, 3-hydroxyquinidine (t 1/2
= 12 ± 3 hours; percent bound in plasma = 60 ±
10%). b Metabolically cleared primarily by CYP3A. c Following a 400-mg IV dose (22-minute
infusion) of quinidine gluconate or a single 400-mg oral dose of immediate-release (IR)
quinidine sulfate or a 300-mg dose of extended-release (ER) quinidine sulfate (QUINIDEX) to
healthy adults. Specific assay methods for quinidine show >75% reduction in frequency of
premature ventricular contractions at levels of 0.7-5.9 μg/mL, but active metabolite was not
measured; therapeutic levels of 2-7 μg/mL were reported for nonspecific assays.
Quinine a
References: Brosen K, et al. Quinidine kinetics after a single oral dose in relation to the
sparteine oxidation polymorphism in man. Br J Clin Pharmacol, 1990, 29:248–253. Sawyer
WT, et al. Bioavailability of a commercial sustained-release quinidine tablet compared to oral
quinidine solution. Biopharm Drug Dispos, 1982, 3:301–310. Ueda CT, et al. Absolute quinidine
bioavailability. Clin Pharmacol Ther, 1976, 20:260–265.
76 ± 11 N-A: 12-20 N-A: ~85-90 b N-A: 1.9 ± 0.5 N-A: 1.8 ± 0.4 N-A: 11 ± 2 PO: 3.5-8.4 d Adults
M-A: 33 ± 18 M-A: 93-95 b M-A: 0.9-1.4 M-A: 1.0-1.7 M-A: 11-18 IV: 11 ± 2 μg/mL d
b Neo M-C: 0.4-1.4 M-C: 1.2-1.7 M-C: 12-16 PO: 7.3-9.4 μg/mL d
i Preg i Preg, c RD c b Preg c b Preg, c Smk Children
a Smk i RD c i RD c IV: 8.7-9.4 μg/mL d
b Aged a Hep, Aged PO: 7.3 ± 1.1 μg/mL d
a
Data from normal adults (N-A) and range of means from different studies of adults (M-A) or
children (M-C) with malaria reported. b Correlates with serum α 1
-acid glycoprotein levels.
Binding is increased in severe malaria. c From patients with malaria. d Following a single
10-mg/kg dose given as a 0.5- to 4-hour IV infusion or orally (PO) to children or adults with
malaria. A level >0.2 μg/mL for unbound drug is targeted for treatment of falciparum malaria.
Oculotoxicity and hearing loss/tinnitus associated with unbound concentrations >2 μg/mL.
References: Edwards G, et al. Clinical pharmacokinetics in the treatment of tropical diseases.
Some applications and limitations. Clin Pharmacokinet, 1994, 27:150–165. Krishna S, et al.
Pharmacokinetics of quinine, chloroquine and amodiaquine. Clinical implications. Clin
Pharmacokinet, 1996, 30:263–299.