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
Ceftriaxone a
IM: ~100% 43 ± 10 b 96% (0.5 μg/ 0.5 g: 0.22 ± 0.5 g: 0.12 ± 5.9-6.5 e IM: 2 IV h
mL) to 83% 0.04 0.02 0.5 g: 101 ±
(300 μg/mL) c 2 g: 0.28 ± 2 g: 0.14 ± 13 μg/mL
0.04 e 0.01 e 2.0 g: 280 ±
39 μg/mL
IM h
Celecoxib a
b RD f
a RD f
b LD d b LD d i LD g
a
Ceftriaxone is most commonly administered by IV or IM injection and cleared unchanged by
both renal and biliary excretion. b Value for a 2-g IV dose; similar values reported for 0.5- and
1-g doses. c Exhibits saturable binding. d Study in patients with mild to severe hepatic impairment.
e Total clearance and distribution volume vary with dose and plasma free fraction; however,
the unbound concentration at steady state is dose proportional. Mean t 1/2
values for 0.5-
to 2-g doses not significantly different. f Study in anephric patients with normal nonrenal
clearance. Much greater increases seen in patients with both renal and hepatic disease.
0.5 g: 65 μg/mL
1.0 g: 114 μg/mL
— <3 ~97 6.60 ± 1.85 c 6.12 ± 2.08 c 11.2 ± 3.47 2.8 ± 1.0 f 705 ± 268 ng/mL f
a Food b b Aged, LD d a Food
a RD e
a
Data from healthy subjects. Cleared primarily by CYP2C9 (polymorphic). b High-fat meal.
Absolute bioavailability is unknown. c CL/F and V/F values reported. d CL/F reduced, mild or
moderate hepatic impairment. e CL/F increased, moderate renal impairment, but unrelated to
CL cr
. f Following a single 200-mg oral dose.
Cephalexin
g
Impact of liver disease is limited by apparent offsetting changes in plasma-free fraction and
unbound intrinsic clearance. h Following twice-daily dosing to steady state.
References: Patel IH, et al. Pharmacokinetics of ceftriaxone in humans. Antimicrob Agents
Chemother, 1981, 20:634–641. Pollock AA, et al. Pharmacokinetic characteristics of intravenous
ceftriaxone in normal adults. Antimicrob Agents Chemother, 1982, 22:816–823. Yuk
JH, et al. Clinical pharmacokinetics of ceftriaxone. Clin Pharmacokinet, 1989, 17:223–235.
References: Goldenberg MM. Celecoxib, a selective cyclooxygenase-2 inhibitor for the treatment
of rheumatoid arthritis and osteoarthritis. Clin Ther, 1999, 21:1497–1513; discussion
1427–1428. PDR54, 2000, p. 2334.
90 ± 9 91 ± 18 14 ± 3 4.3 ± 1.1 a 0.26 ± 0.03 a 0.90 ± 0.18 1.4 ± 0.8 a 28 ± 6.4 μg/mL a
b RD i RD a RD
a
Following a single 500-mg oral dose given to healthy male adults.
Reference: Spyker DA, et al. Pharmacokinetics of cefaclor and cephalexin: Dosage nomograms
for impaired renal function. Antimicrob Agents Chemother, 1978, 14:172–177.