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

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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
Diltiazem a
38 ± 11 <4 78 ± 3 11.8 ± 2.2 b 3.3 ± 1.2 4.4 ± 1.3 c 4.0 ± 0.4 d 151 ± 46 ng/mL d
i Aged i Aged i RD, Aged
b RD
b RD
a
Active metabolites, desacetyldiltiazem (t 1/2
= 9 ± 2 hours) and N-desmethyldiltiazem (t 1/2
= 7.5
± 1 hour). Formation of desmethyl metabolite (major pathway of CL) catalyzed primarily by
CYP3A. b More than a 2-fold decrease with multiple dosing. c t 1/2
for oral dose is 5-6 hours;
does not change with multiple dosing. d Following a single 120-mg oral dose to healthy adults.
Diphenhydramine
72 ± 26 1.9 ± 0.8 78 ± 3 6.2 ± 1.7 a 4.5 ± 2.8 a,b 8.5 ± 3.2 a PO: 2.3 ± 0.64 c IV: ~230 ng/mL c
i LD b LD i LD i LD a LD, Aged PO: 66 ± 22 ng/mL c
a Child
b Child
b Aged
a
Increased CL, decreased V, and no change in t 1/2
in Asians, presumably due to decreased
plasma protein binding. b V area
reported. c Following a single 50-mg dose of diphenhydramine
hydrochloride (44-mg base) given IV or orally to fasted healthy adults. Levels >25 ng/mL
provide antihistaminic effect, whereas levels >60 ng/mL are associated with drowsiness and
mental impairment.
Docetaxel a
Reference: Echizen H, et al. Clinical pharmacokinetics of verapamil, nifedipine, and diltiazem.
Clin Pharmacokinet, 1986, 11:425–449.
Reference: Blyden GT, et al. Pharmacokinetics of diphenhydramine and a demethylated
metabolite following intravenous and oral administration. J Clin Pharmacol, 1986,
26:529–533.
— 2.1 ± 0.2 94 22.6 ± 7.7 L/hr/m 2 72 ± 24 L/m 2 13.6 ± 6.1 — 2.4 ± 0.9 μg/mL c
b LD b
a
Data from male and female patients treated for cancer. Metabolized by CYP3A and excreted
into bile. Parenteral administration. b Mild to moderate liver impairment. c Following an IV
infusion of 85 mg/m 2 over 1.6 hours.
References: Clarke SJ, et al. Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet,
1999, 36:99–114. Extra JM, et al. Phase I and pharmacokinetic study of Taxotere (RP 56976;
NSC 628503) given as a short intravenous infusion. Cancer Res, 1993, 53:1037–1042. PDR54,
2000, p. 2578.