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

Spironolactone a
— b <1 c >90 d 93 e 10 e S: 1.3 ± 0.3 f S: 1.0 f S: 185 ± 51 ng/mL f
a Food C: 11.2 ± 2.3 f C: 2.9 ± 0.6 f C: 231 ± 49 ng/mL f
a
Spironolactone (S) is extensively metabolized; it has three known active metabolites: canrenone
(C), 7α-thiomethylspironolactone (TS), and 6β-hydroxy-7α-thiomethylspironolactone
(HTS). b Absolute bioavailability is not known; old values reported in the literature were based
on nonspecific assays for C; likely to exhibit first-pass metabolism. AUC of parent drug and
metabolites increased when S taken with food. c Measured after an oral dose. d Binding of S
and its active metabolites. e CL/F and V area
/F; calculated from reported AUC and t 1/2
data.
f
Following a single 200-mg oral dose of S. C accumulates 2.5-fold with multiple S dosing.
g
t 1/2
of parent drug and metabolites increased in patients with cirrhosis.
Streptokinase a
TS: 2.8 ± 0.4 f TS: 1.8 ± 0.5 f TS: 571 ± 74 ng/mL f
HTS: 10.1 ± 2.3 f HTS: 3.1 ± 0.9 f HTS: 202 ± 54 ng/mL f
a LD g
References: Ho PC, et al. Pharmacokinetics of canrenone and metabolites after base hydrolysis
following single and multiple dose oral administration of spironolactone. Eur J Clin
Pharmacol, 1984, 27:441–446. Overdiek HW, et al. Influence of food on the bioavailability of
spironolactone. Clin Pharmacol Ther, 1986, 40:531–536. Overdiek HW, et al. New insights
into the pharmacokinetics of spironolactone. Clin Pharmacol Ther, 1985, 38:469–474.
PDR54, 2000, p. 2883. Sungaila I, et al. Spironolactone pharmacokinetics and pharmacodynamics
in patients with cirrhotic ascites. Gastroenterology, 1992, 102:1680–1685.
— 0 — 1.7 ± 0.7 0.08 ± 0.04 b 0.61 ± 0.24 0.9 ± 0.21 c 188 ± 58 IU/mL c
a
Values obtained from acute MI patients using a function bioassay. b V area
reported. c Following
a single 1.5 × 10 6 IU IV dose given as a 60-minute infusion to patients with acute MI.
Reference: Gemmill JD, et al. A comparison of the pharmacokinetic properties of streptokinase
and anistreplase in acute myocardial infarction. Br J Clin Pharmacol, 1991, 31:143–147.
Sulfamethoxazole
~100 14 ± 2 53 ± 5 0.31 ± 0.07 a,b 0.26 ± 0.04 a 10.1 ± 2.6 a 4 b 37.1 μg/mL b
b RD, Alb i RD a RD a RD
i Aged, CF a CF i Child, CF i Child
b CF
a
Studies include concurrent administration of trimethoprim and variation in urinary pH; these
factors had no marked effect on the CL of sulfamethoxazole. Metabolically cleared primarily
by N 4
-acetylation. b Following a single 1000-mg oral dose given to healthy adults.
Sumatriptan
References: Hutabarat RM, et al. Disposition of drugs in cystic fibrosis. I. Sulfamethoxazole
and trimethoprim. Clin Pharmacol Ther, 1991, 49:402–409. Welling PO, et al.
Pharmacokinetics of trimethoprim and sulfamethoxazole in normal subjects and in patients
with renal failure. J Infect Dis, 1973, 128(suppl):556–566.
PO: 14 ± 5 22 ± 4 14-21 22 ± 5.4 2.0 ± 0.34 1.0 ± 0.3 a SC: 0.2 SC: 72 (55-108)
(0.1-0.3) b ng/mL b
SC: 97 ± 16
PO: ~1.5 b PO: 54 (27-137)
ng/mL b
a
An apparent t 1/2
of ~2 hours reported for SC and oral doses. b Following a single 6-mg SC or
100-mg oral dose given to healthy young adults.
References: Scott AK. Sumatriptan clinical pharmacokinetics. Clin Pharmacokinet, 1994,
27:337–344. Scott AK, et al. Sumatriptan and cerebral perfusion in healthy volunteers. Br J
Clin Pharmacol, 1992, 33:401–404.
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