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

1984
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
Tramadol a
70-75 10-30 b 20 8 (6-12) 2.7 (2.3-3.9) 5.5 (4.5-7.5) T: 2.3 ± 1.4 c T: 592 ± 178 ng/mL c
b LD, RD a RD, LD Ml: 2.4 ± 1.1 c Ml: 110 ± 32 ng/mL c
a
Tramadol (T) is available as a racemic mixture. At steady state, the plasma concentration of
(+) (1R,2R)-tramadol is ~30% higher than that of (−) (1S,2S)-tramadol. Both isomers contribute
to analgesia. Data reported are for total (+ and −) T. T is metabolized by CYP2D6 to
an active O-desmethyl metabolite (M1); there are other CYP-catalyzed metabolites. b Recovery
Trazodone a
81 ± 6 <1 93 2.1 ± 0.1 1.0 ± 0.1 d 5.9 ± 0.4 2.0 ± 1.5 e 1.5 ± 0.2 μg/mL e
i Aged, Obes b Aged, b Obes c a Aged, Obes a Aged, Obes
a
Active metabolite, m-chlorophenylpiperazine, is a tryptaminergic agonist; formation catalyzed
by CYP3A. b Significant for male subjects only. c No difference when CL is normalized
to ideal body weight. d V area
reported. e Following a single 100-mg oral dose (capsule) given
with a standard breakfast to healthy adults.
Triamterene a
following an oral dose was reported. c Following a 100-mg immediate-release tablet given
every 6 hours for 7 days.
References: Klotz U. Tramadol—The impact of its pharmacokinetic and pharmacodynamic
properties on the clinical management of pain. Arzneimittelforschung, 2003, 53:681–687.
PDR58, 2004, p. 2494.
References: Greenblatt DJ, et al. Trazodone kinetics: Effect of age, gender, and obesity. Clin
Pharmacol Ther, 1987, 42:193–200. Nilsen OG, et al. Single dose pharmacokinetics of trazodone
in healthy subjects. Pharmacol Toxicol, 1992, 71:150–153.
51 ± 18 b 52 ± 10 b 61 ± 2 d 63 ± 20 f 13.4 ± 4.9 4.2 ± 0.7 g T: 2.9 ± 1.6 h Y, T: 26.4 ± 17.7
ng/mL h
b LD c a HL b LD, RD, e Aged e a RD e TS: 4.1 ± 2.0 h Y, TS: 779 ±
i Aged b b RD, 310 ng/mL h
Alb, LD e
E, T: 84 ± 91 ng/mL h
a
Active metabolite, hydroxytriamterene sulfuric acid ester (TS). b Triamterene (T) plus active
metabolite. c Decreased active metabolite; increased parent drug. d For metabolite, percent
bound = 90.4 ± 1.3. e Active metabolite. f Because T is predominantly present in plasma as the
active metabolite, this value is deceptively high. CL renal
= 2.3 ± 0.6 for the metabolite.
g
Metabolite t 1/2
= 3.1 ± 1.2 hours. h Data for T and TS following a single 50-mg oral dose taken
after a fast by young healthy volunteers (Y) and elderly patients requiring diuretic therapy (E).
E, TS: 526 ± 388
ng/mL h
References: Gilfrich HJ, et al. Pharmacokinetics of triamterene after i.v. administration to
man: Determination of bioavailability. Eur J Clin Pharmacol, 1983, 25:237–241. Muhlberg
W, et al. Pharmacokinetics of triamterene in geriatric patients—Influence of piretanide and
hydrochlorothiazide. Arch Gerontol Geriatr, 1989, 8:73–85.