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
Exenatide a
SC: ~100 — — 8.1 b 0.1 c 1.5 (0.9-2.0) 2 (1-3) c 821 ± 500 pg/mL d
b RD
a RD
a
Exenatide is a synthetic peptide cleared primarily by the kidney through filtration, reabsorption,
and proteolytic degradation. b CL/F after SC injection reported. c V area
/F after SC injection
reported. d Following a 10-μg SC injection.
Ezetimibe a
— ~2 >90 b 6.6 c 1.5 c 28-30 d 1 e 122 ng/mL e
b Aged,
RD, LD
a
Ezetimibe is extensively metabolized to a glucuronide, which is more active than ezetimibe
in inhibiting cholesterol absorption. Clinical effects are related to the total plasma concentration
of ezetimibe and ezetimibe–glucuronide, with ezetimibe concentrations being only 10%
of the total. b For ezetimibe and ezetimibe–glucuronide. c CL/F and a volume for the central
compartment (V c
/F) for total (unconjugated and glucuronide conjugate) ezetimibe reported.
d
Ezetimibe undergoes significant enterohepatic recycling, leading to multiple secondary
Famotidine a
References: Linnebjerg H, et al. Effects of renal impairment on the pharmacokinetics of exenatide.
Br J Clin Pharmacol, 2007, 64:317–327.
peaks. An effective t 1/2
is estimated. e Total (unconjugated and glucuronide conjugate) ezetimibe
following a 10-mg oral dose given once daily for 10 days.
References: Mauro VF, et al. Ezetimibe for management of hypercholesterolemia. Ann
Pharmacother, 2003, 37:839–848. Patrick JE, et al. Disposition of the selective cholesterol
absorption inhibitor ezetimibe in healthy male subjects. Drug Metab Dispos, 2002,
30:430–437. PDR58, 2004, pp. 3085–3086.
37 (20-66) 65-80 20 4.3-6.9 b 1.1-1.4 2.5-4.0 2.3 (1-4) 76-104 ng/mL d
b Aged, RD,
a RD
Neo c
a
Cleared primarily by the kidney. b Renal clearance after IV administration was ~4.3 mL/min/kg.
c
The pharmacokinetics of IV famotidine were similar in children >1 year of age and adults.
d
Following a single 40-mg oral dose.
References: Krishna DR, et al. Newer H2-receptor antagonists. Clinical pharmacokinetics and
drug interaction potential. Clin Pharmacokinet, 1988, 15:205–215. Maples HD, et al.
Famotidine disposition in children and adolescents with chronic renal insufficiency. J Clin
Pharmacol, 2003, 43:7–14. Wenning LA, et al. Pharmacokinetics of famotidine in infants.
Clin Pharmacokinet, 2005, 44:395–406.