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
Gemcitabine a
— <10 Negligible 37.8 ± 19.4 b 1.4 ± 1.3 c 0.63 ± 0.48 c — 26.9 ± 9 μM d
b Aged
a Aged
a
Data from patients with leukemia. Rapidly metabolized intracellularly to active di- and
triphosphate products; IV administration. b Weight-normalized CL is ~25% lower in women,
compared to men. c V d
and t 1/2
are reported to increase with long duration of IV infusion.
d
Steady-state concentration during a 10-mg/m 2 /min infusion for 120-640 minutes.
Gemfibrozil
98 ± 1 <1 97 1.7 ± 0.4 0.14 ± 0.03 1.1 ± 0.2 1-2 a 15-25 μg/mL a
i LD, RD
i RD
a
Following a 600-mg oral dose given twice daily to steady state.
Gentamicin
IM: ~100 >90 <10 CL = 0.82CL cr
+ 0.11 0.31 ± 0.10 2-3 a IV: 1 b IV: 4.9 ± 0.5 μg/mL b
i RD, Aged, IM: 0.3-0.75 b IM: 5.0 ± 0.4 μg/mL b
CF, Child
b Obes
b Obes
a Neo
a
Gentamicin has a very long terminal t 1/2
of 53 ± 25 hours (slow release from tissues), which
accounts for urinary excretion for up to 3 weeks after a dose. b Following a single
100-mg IV infusion (1 hour) or IM injection given to healthy adults.
Glimepiride a
References: Grunewald R, et al. Gemcitabine in leukemia: A phase I clinical, plasma, and cellular
pharmacology study. J Clin Oncol, 1992, 10:406–413. PDR54, 2000, p. 1586.
Reference: Todd PA, et al. Gemfibrozil. A review of its pharmacodynamic and pharmacokinetic
properties, and therapeutic use in dyslipidaemia. Drugs, 1988, 36:314–339.
References: Matzke GR, et al. Pharmacokinetics of cetirizine in the elderly and patients with
renal insufficiency. Ann Allergy, 1987, 59:25–30. Regamey C, et al. Comparative pharmacokinetics
of tobramycin and gentamicin. Clin Pharmacol Ther, 1973, 14:396–403.
~100 <0.5 >99.5 0.62 ± 0.26 0.18 3.4 ± 2.0 2-3 c 359 ± 98 ng/mL c
a RD b a RD b i RD b
a
Data from healthy male subjects. No significant gender differences. Glimepiride is metabolized
by CYP2C9 to an active (approximately one-third potency) metabolite, Ml. b CL/F, V d
/F
increased and t 1/2
unchanged, moderate to severe renal impairment; presumably mediated
through an increase in plasma-free fraction. Ml AUC also increased. c Following a single 3-mg
oral dose.
References: Badian M, et al. Determination of the absolute bioavailability of glimepiride
(HOE 490), a new sulphonylurea. Int J Clin Pharmacol Ther Toxicol, 1992, 30:481–482.
PDR54, 2000, pp. 1346–1349. Rosenkranz B, et al. Pharmacokinetics and safety of
glimepiride at clinically effective doses in diabetic patients with renal impairment.
Diabetologia, 1996, 39:1617–1624.