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
Atorvastatin a
12 <2 ≥98 29 b ~5.4 b 19.5 ± 9.6 2.3 ± 0.96 d 14.9 ± 1.8 ngEq/mL d
b LD, c Aged
a LD, b Aged
i RD
a
Data from healthy adult male and female subjects. No clinically significant gender differences.
Atorvastatin undergoes extensive CYP3A-dependent first-pass metabolism.
Metabolites are active and exhibit a longer t 1/2
(20-30 hours) than parent drug. b Mean CL/F
parameter calculated from reported AUC data at steady state after a once-a-day 20-mg oral
dose, assuming a 70-kg body weight. c AUC following oral administration increased, mild to
moderate hepatic impairment. d Following a 20-mg oral dose once daily for 14 days.
Azathioprine a
60 ± 31 b <2 — 57 ± 31 c 0.81 ± 0.65 c 0.16 ± 0.07 c MP: l-2 d MP: 20-90 ng/mL d
a
Azathioprine is metabolized to mercaptopurine (MP), listed later in this table. b Determined as
the bioavailability of MP; intact azathioprine is undetectable after oral administration because of
extensive first-pass metabolism. Kinetic values are for IV azathioprine. c Data from kidney
Azithromycin
34 ± 19 12 7-50 a 9 31 40 b 2-3 c 0.4 μg/mL c
b Food (capsules)
i LD
a Food (suspension)
a
Dose-dependent plasma binding. The bound fraction is 50% at 50 ng/mL and 12% at 500
ng/mL. b A longer terminal plasma t 1/2
of 68 ± 8 hours, reflecting release from tissue stores,
overestimates the multiple-dosing t 1/2
. c Following a 250-mg/day oral dose to adult patients
with an infection.
Baclofen a
References: Gibson DM, et al. Effect of age and gender on pharmacokinetics of atorvastatin in
humans. J Clin Pharmacol, 1996, 36:242–246. Lea AP, et al. Atorvastatin. A review of its
pharmacology and therapeutic potential in the management of hyperlipidaemias. Drugs, 1997,
53:828–847. PDR54, 2000, p. 2254.
>70 b 69 ± 14 31 ± 11 2.72 ± 0.93 c 0.81 ± 0.12 c 3.75 ± 0.96 1.0 (0.5-4) e 160 ± 49 ng/mL e
b RD d
a
Data from healthy adult male subjects. b Bioavailability estimate based on urine recovery of
unchanged drug after oral dose. c CL/F, V area
/F reported for intestinal infusion of drug. d Limited
data suggest CL/F reduced with renal impairment. e Following a single 10-mg oral dose.
i RD
transplant patients. d MP concentration following a 135 ± 34-mg oral dose of azathioprine given
daily to steady state in kidney transplant patients.
Reference: Lin SN, et al. Quantitation of plasma azathioprine and 6-mercaptopurine levels in
renal transplant patients. Transplantation, 1980, 29:290–294.
Reference: Lalak NJ, et al. Azithromycin clinical pharmacokinetics. Clin Pharmacokinet,
1993, 25:370–374.
References: Kochak GM, et al. The pharmacokinetics of baclofen derived from intestinal infusion.
Clin Pharmacol Ther, 1985, 38:251–257. Wuis EW, et al. Plasma and urinary excretion
kinetics of oral baclofen in healthy subjects. Eur J Clin Pharmacol, 1989, 37:181–184.