DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1990
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
Zidovudine
63 ± 10 18 ± 5 <25 26 ± 6 a 1.4 ± 0.4 1.1 ± 0.2 0.5-l c IV: 2.6 μg/mL c
a Neo b RD, b Neo, LD b RD, b LD i RD, Preg PO: 1.6 μg/mL c
i Preg i Child, Preg i Child, Preg a Neo, LD
a
Formation of 5-O-glucuronide is the major route of elimination (68%). b A change in CL/F
and V area
/F reported. c Following a 5-mg/kg IV or oral dose given every 4 hours to steady state.
Ziprasidone a
PO: 59 <l b 99.9 ± 0.08 11.7 2.3 2.9 c PO: 4 ± l d PO: 68 ± 20 ng/mL d
a Food IM: 0.7 e IM: 156 ng/mL e
IM: 100
a
Approximately one-third of the dose is oxidized by CYP3A4, and the remainder undergoes
reduction. b Recovery following oral administration. c A longer t 1/2
after oral dosing is rate limited
by absorption; food decreases apparent t 1/2
. In the elderly, the t 1/2
is slightly longer.
d
Following a 20-mg oral dose given twice daily for 8 days. e Following a single 10-mg IM
dose.
Zolpidem
72 ± 7 <1 92 4.5 ± 0.7 a 0.68 ± 0.06 1.9 ± 0.2 1.0-2.6 b 76-139 ng/mL b
a RD, LD i RD a RD a Aged, LD a Food b Food
b LD, Aged
i RD
a Child
b Child
a
Metabolically cleared predominantly by CYP3A4. b Following a single 10-mg oral dose given
to young adults. No accumulation of drug with once-daily dosing.
References: Greenblatt DJ, et al. Comparative kinetics and dynamics of zaleplon, zolpidem,
and placebo. Clin Pharmacol Ther, 1998, 64:553–561. Patat A, et al. EEG profile of
Zonisamide a
References: Blum MR, et al. Pharmacokinetics and bioavailability of zidovudine in humans.
Am J Med, 1988, 85:189–194. Morse GD, et al. Comparative pharmacokinetics of antiviral
nucleoside analogues. Clin Pharmacokinet, 1993, 24:101–123.
References: Gunasekara NS, et al. Ziprasidone: A review of its use in schizophrenia and
schizoaffective disorder. Drugs, 2002, 62:1217–1251. Miceli JJ, et al. Single- and multipledose
pharmacokinetics of ziprasidone under nonfasting conditions in healthy male volunteers.
Br J Clin Pharmacol, 2000, 49(suppl):5S–13S. PDR58, 2004, p. 2598. Wilner KD, et al.
Single- and multiple-dose pharmacokinetics of ziprasidone in healthy young and elderly
volunteers. Br J Clin Pharmacol, 2000, 49(suppl):15S–20S.
intravenous zolpidem in healthy volunteers. Psychopharmacology (Berl), 1994, 114:138–146.
Salva P, et al. Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic
implications. Clin Pharmacokinet, 1995, 29:142–153.
— b 29-48 c 38-40 d 0.13 e 1.2-1.8 f 63 ± 14 1.8 ± 0.4 g 28 ± 4 μg/mL g
a
Primary routes of metabolism involve reductive cleavage of the isoxazole ring (CYP3A4)
and N-acetylation. b Absolute bioavailability is not known; minimum equal to urine recovery
after an oral dose. c Recovery following an oral dose. d Concentrates in erythrocytes to as much
as 8-fold. e Steady-state CL/F for a 400-mg once-daily dose reported. AUC increases disproportionately
when the dose is increased from 400-800 mg. f V/F for a single dose is reported;
decreases as the dose is increased from 200-800 mg. g Following a 400-mg oral dose given
once daily to steady state in healthy adults.
References: Kochak GM, et al. Steady-state pharmacokinetics of zonisamide, an antiepileptic
agent for treatment of refractory complex partial seizures. J Clin Pharmacol, 1998, 38:166–171.
Peters DH, et al. Zonisamide. A review of its pharmacodynamic and pharmacokinetic properties,
and therapeutic potential in epilepsy. Drugs, 1993, 45:760–787. PDR58, 2004, p. 1232.