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

Pseudoephedrine a
~100 43-96 b — 7.33 b,c 2.64-3.51 c 4.3-8 b,c IR: 1.4-2 d IR: 177-360 ng/mL d
a
Data from healthy adult male and female subjects. b At a high urinary pH (>7.0), pseudoephedrine
is extensively reabsorbed; t 1/2
increases, and CL decreases. c CL/F, V/F, and t 1/2
reported for oral dose. d Range of mean values from different studies following a single 60-mg
immediate-release tablet or syrup (IR), or 120-mg controlled-release capsule (CR) oral dose.
Pyrazinamide a
CR: 3.8-6.1 d
CR: 265-314 ng/mL d
— b 4-14 c 10 1.1 (0.2-2.3) d 0.57 (0.13-1.04) d 6 (2-23) 1-2 e 35 (19-103) μg/mL e
a Child
b Child
a
Pyrazinamide is hydrolyzed in the liver to an active metabolite, 2-pyrazinoic acid. Reported peak
2-pyrazinoic acid concentrations range from 0.1- to 1-fold that of the parent drug. Pyrazinamide
data reported are for male and female adults with tuberculosis. b Absolute bioavailability is not
known, but the drug is well absorbed based on recovery of parent drug and metabolites (70%).
c
Recovery unchanged following an oral dose; the recovery of pyrazinoic acid is 37 ± 5%. d CL/F
and V area
/F reported. e Following a 15- to 53-mg/kg daily oral dose to steady state.
Quetiapine a
9 <1% 83 19 10 ± 4 6 1-1.8 278 ng/mL b
a Food
b Aged
i RD
b LD
a
No significant gender differences. Extensively metabolized through multiple pathways, including
sulfoxidation, N- and O-dealkylation catalyzed by CYP3A4. Two minor active metabolites.
b
Following a 250-mg oral dose given daily for 23 days in patients with schizophrenia.
Quinapril a
Reference: Kanfer I, et al. Pharmacokinetics of oral decongestants. Pharmacotherapy, 1993,
13:116S–128S.
References: Bareggi SR, et al. Clinical pharmacokinetics and metabolism of pyrazinamide
in healthy volunteers. Arzneimittelforschung, 1987, 37:849–854. Lacroix C, et al.
Pharmacokinetics of pyrazinamide and its metabolites in healthy subjects. Eur J Clin
Pharmacol, 1989, 36:395–400. PDR58, 2004, p. 766. Zhu M, et al. Population pharmacokinetic
modeling of pyrazinamide in children and adults with tuberculosis. Pharmacotherapy,
2002, 22:686–695.
QT (Q): 52 ± 15 b Q (Q): 3.1 ± 1.2 c Q/QT: 97 QT (QT): QT (QT): Q (Q): 0.8-0.9 c Q (Q): Q (Q): 207 ±
0.98 ± 0.22 d 0.19 ± 0.04 d 1.4 ± 0.8 e 89 ng/mL e
QT (QT): 96 d QT (QT): QT (Q): QT (Q): 923 ±
2.1-2.9 d 2.3 ± 0.9 e 277 ng/mL e
b RD
a RD
a
Hydrolyzed to its active metabolite, quinaprilat. Pharmacokinetic data for quinapril (Q) and
quinaprilat (QT) following oral Q and IV QT administration are presented. b Absolute
bioavailability based on plasma QT concentrations. c Data for Q following a 2.5- to 80-mg oral
Q dose. d Data for QT following a 2.5-mg IV QT dose. The t 1/2
of QT after dosing Q is similar.
e
Following a single 40-mg oral Q dose. No accumulation of QT with multiple dosing.
References: Goren JL, et al. Quetiapine, an atypical antipsychotic. Pharmacotherapy, 1998,
18:1183–1194. PDR54, 2000, p. 563.
References: Breslin E, et al. A pharmacodynamic and pharmacokinetic comparison of intravenous
quinaprilat and oral quinapril. J Clin Pharmacol, 1996, 36:414–421. Olson SC, et al.
The clinical pharmacokinetics of quinapril. Angiology, 1989, 40:351–359. PDR58, 2004,
p. 2516.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1969