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
Metronidazole a
99 ± 8 b 10 ± 2 11 ± 3 1.3 ± 0.3 0.74 ± 0.10 8.5 ± 2.9 IV: 27 (11-41) μg/mL c
i Crohn b LD, Neo i RD, a Neo, LD
Crohn, LD
i Preg, RD, i Preg, RD, PO: 2.8 c PO: 19.8 μg/mL c
Crohn, Aged Crohn, Child VA: 11 ± 2 c VA: 1.9±0.2 μg/mL c
a
Active hydroxylated metabolite accumulates in renal failure. b Bioavailability is 67-82% for
rectal suppositories and 53 ± 16% for intravaginal gel. c Following a single 100-mg dose of
vaginal (VA) cream, a 100-mg IV infusion over 20 minutes three times daily to steady state, or
a 100-mg oral dose three times daily to steady state.
Micafungin a
— <1 99 0.14 ± 0.03 0.20 ± 0.03 14.6 ± 3.0 — 8.8 ± 1.8 μg/mL d
i LD b , RD c
a
Undergoes arylsulfatase-dependent metabolism and biliary excretion. b Study in patients with
moderate liver impairment; no difference in weight-adjusted clearance. c Study in patients with
CL cr
<30 mL/min. d Following a 100-mg IV infusion administered over 1 hour.
Midazolam a
Reference: Lau AM, et al. Clinical pharmacokinetics of metronidazole and other nitroimidazole
anti-infectives. Clin Pharmacokinet, 1992, 23:328–364.
Reference: Hebert MF, et al. Pharmacokinetics of micafungin in healthy volunteers, volunteers
with moderate liver disease and volunteers with renal dysfunction. J Clin Pharmacol,
2005, 45:1145–1152.
44 ± 17 b <1% 98 6.6 ± 1.8 1.1 ± 0.6 1.9 ± 0.6 IV: 113 ± 16 ng/mL d
a LD b Aged, RD a RD c a Obes a Aged, PO: 0.67 ± 0.45 d PO: 78 ± 27 ng/mL d
Obes, LD
i Smk, LD b LD, Neo i LD i Smk
i Obes,
b Neo
Smk, Child
a
Metabolically cleared exclusively by CYP3A. b Undergoes extensive first-pass metabolism by
intestinal and hepatic CYP3A. Bioavailability appears to be dose dependent; 35-67% at
15-mg, 28-36% at 7.5-mg, and 12-47% at 2-mg oral dose, possibly due to saturable first-pass
intestinal metabolism. c Increased CL due to increased plasma free fraction; unbound CL is
unchanged. d Following a single 5-mg IV bolus or 10-mg oral dose.
References: Garzone PD, et al. Pharmacokinetics of the newer benzodiazepines. Clin
Pharmacokinet, 1989, 76:337–364. Thummel KE, et al. Oral first-pass elimination of midazolam
involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin Pharmacol
Ther, 1996, 59:491–502.