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

Isoniazid a
— b RA: 7 ± 2 c ~0 RA: 7.4 ± 2.0 d 0.67 ± 0.15 d RA: 1.1 ± 0.1 RA: 1.1 ± 0.5 f RA: 5.4 ± 2.0 μg/mL f
b Food SA: 29 ± 5 c SA: 3.7 ± 1.1 d i Aged, RD SA: 3.1 ± 1.1 SA: 1.1 ± 0.6 f SA: 7.1 ± 1.9 μg/mL f
i Aged
a AVH, LD,
b RD e
Neo, RD
i Aged, Obes,
Child, HTh
a
Metabolized by NAT 2 (polymorphic). Data for slow acetylators (SA) and rapid acetylators
(RA) reported. b It is usually stated that isoniazid is completely absorbed; however, good estimates
of possible loss due to first-pass metabolism are not available. Absorption is decreased
by food and antacids. c Recovery after oral administration; assay includes unchanged drug and
acid-labile hydrazones. Higher percentages have been noted after IV administration,
Isosorbide Dinitrate a
PO: 22 ± 14 b <1 28 ± 12 46(38-59) c 3.1 (2.2-8.6) 0.7 (0.6-2.0) c IR d IR d
i CHF, RD, Smk
a LD
SL: 45 ± 16 b b LD i RD, Fem ISDN: 0.3 ISDN: 42
(0.2-0.5) (59-166) nM
PC: 33 ± 17 b
i Smk, RD,
Fem, CHF
a
Isosorbide dinitrate (ISDN) is metabolized to the 2- and 5-mononitrates (IS-2-MN and IS-5-
MN). Both metabolites and the parent compound are thought to be active. Data for the dinitrate
are reported except where indicated. b Bioavailability calculations from single dose. SL,
sublingual; PC, percutaneous. c CL may be decreased and t 1/2
prolonged after chronic dosing.
d
Mean (range) for ISDN and IS-2-MN and IS-5-MN following a single 20-mg oral immediate-release
(IR) and sustained-release (SR) dose.
suggesting significant first-pass metabolism. d CL/F and V ss
/F reported. e Decrease in CL NR
/F
as well as CL R
. f Following a single 400-mg oral dose to healthy RAs and SAs.
Reference: Kim YG, et al. Decreased acetylation of isoniazid in chronic renal failure. Clin
Pharmacol Ther, 1993, 54:612–620.
IS-2-MN: 0.6 IS-2-MN: 207
(0.2-1.6) (197-335) nM
IS-5-MN: IS-5-MN: 900
0.7 (0.3-1.9) (790-1080) nM
SR d
SR d
ISDN: ~0 ISDN: ~0
IS-2-MN: 2.8 IS-2-MN: 28
(2.7-3.7) (23-33) nM
IS-5-MN: 5.1 IS-5-MN: 175
(4.2-6.6) (154-267) nM
References: Abshagen U, et al. Pharmacokinetics and metabolism of isosorbide-dinitrate after
intravenous and oral administration. Eur J Clin Pharmacol, 1985, 27:637–644. Fung HL.
Pharmacokinetics and pharmacodynamics of organic nitrates. Am J Cardiol, 1987, 60:4H–9H.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1943