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

1986
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
Valproic Acid a
100 ± 10 b 1.8 ± 2.4 93 ± l c 0.11 ± 0.02 d,e 0.22 ± 0.07 14 ± 3 d,e l-4 f 34 ± 8 μg/mL f
b RD, LD, a Child a LD, Neo a LD, Neo
Preg, Aged,
Neo, Burn,
Alb
i LD, Aged i Aged, Child b Child
i Aged
a
Valproic acid is available either as the free acid or stable coordination compound comprised
of sodium valproate and valproic acid (divalproex sodium). b Systemic availability of valproate
ion is the same after molar equivalent oral doses of free acid and divalproex sodium. c Dose
dependent; value shown for daily doses of 250 and 500 mg. At 1 g daily, percent bound = 90 ±
2%. d Data for multiple dosing (500 mg daily) reported. Single-dose value: 0.14 ± 0.04
mL/min/kg; t 1/2
= 9.8 ± 2.6 hours. Total CL is the same at 100 mg daily, although CL of free
drug increases with multiple dosing. e Increased CL and decreased t 1/2
from enzyme induction
following concomitant administration of other anti-epileptic drugs. f average concentration
Valsartan a
following a 250-mg oral dose (capsule, DEPAKENE) given twice daily for 15 days to healthy
male adults. A therapeutic range of 50-150 μg/mL is reported. T max
is 3-8 hours for divalproex
tablets and 7-14 hours for extended-release divalproex tablets.
References: Dean JC. Valproate. In: Wyllie E, ed. The Treatment of Epilepsy, 2nd ed.
Baltimore, Williams & Wilkins, 1997, pp. 824–832. Pollack GM, et al. Accumulation and
washout kinetics of valproic acid and its active metabolites. J Clin Pharmacol, 1986,
26:668–676. Zaccara G, et al. Clinical pharmacokinetics of valproic acid—1988. Clin
Pharmacokinet, 1988, 15:367–389.
23 ± 7 29.0 ± 5.8 95 0.49 ± 0.09 0.23 ± 0.09 9.4 ± 3.8 2 (1.5-3) c 1.6 ± 0.6 μg/mL c
b Food b Aged, LD b a Aged
i RD
a
Data from healthy adult male subjects. No significant gender differences. Valsartan is cleared
primarily by biliary excretion. b CL/F reduced, mild to moderate hepatic impairment and biliary
obstruction. c Following a single 80-mg oral dose (capsule).
References: Brookman LJ, et al. Pharmacokinetics of valsartan in patients with liver disease.
Clin Pharmacol Ther, 1997, 62:272–278. Flesch G, et al. Absolute bioavailability and
pharmacokinetics of valsartan, an angiotensin II receptor antagonist, in man. Eur J Clin
Pharmacol, 1997, 52:115–120. Muller P, et al. Pharmacokinetics and pharmacodynamic
effects of the angiotensin II antagonist valsartan at steady state in healthy, normotensive
subjects. Eur J Clin Pharmacol, 1997, 52:441–449. PDR54, 2000, p. 2015.