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

Felodipine a
15 ± 8 <1 99.6 ± 02 12 ± 5 b 10 ± 3 14 ± 4 IR: 0.9 ± 0.4 d IR: 34 ± 26 nM d
i Aged, Cirr b RD, LD b Aged, LD, CHF c i Aged a Aged, CHF c ER: 3.7 ± 0.9 d ER: 9.1 ± 7.3 nM d
a Food i Aged b LD i LD
Fenofibrate a
— b 0.1-10 c >99 0.45 d 0.89 d 20-27 IR: 6-8 e IR: 8.6 ± 0.9 μg/mL e
a Food b RD a RD Mic: 4-6 f Mic: 10.8 ± 0.6 μg/mL f
a
Fenofibrate is a prodrug that is hydrolyzed by esterases to fenofibric acid, the pharmacologically
active compound. All values reported are for fenofibric acid. b Absolute bioavailability is
not known. Recovery of radiolabeled dose in urine as fenofibric acid and its glucuronide is
60%. Immediate-release (IR) tablet and micronized (Mic) capsule are bioequivalent.
Bioavailability is increased when taken with a standard meal. c Recovery following oral dose.
Fentanyl
TM: ~50 8 84 ± 2 13 ± 2 a 4.0 ± 0.4 3.7 ± 0.4 TD: 35 ± 15 b TD: 1.4 ± 0.5 ng/mL b
b Aged a CPBS, Aged, TM: 0.4 TM: 0.8 ± 0.3 ng/mL b
i Prem, Prem (0.3-6) b
Child
i Child
a Neo
a
Metabolically cleared primarily by CYP3A to norfentanyl and hydroxy metabolites.
b
Following a 5-mg transdermal (TD) dose administered at 50 μg/hr through a DURAGESIC
system or a single 400-μg transmucosal (TM) dose. Postoperative and intraoperative analgesia
occurs at plasma concentrations of 1 ng/mL and 3 ng/mL, respectively. Respiratory depression
occurs >0.7 ng/mL.
Fexofenadine a
a
Racemic mixture; S-(–)-enantiomer is an active Ca +2 channel blocker; different enantiomer
pharmacokinetics result in S-(–)-enantiomer concentrations about 2-fold higher than those of
R-(+)-isomer. b Undergoes significant CYP3A-dependent first-pass metabolism in the intestine
and liver. c May be age related rather than CHF related. d Following a 10-mg oral immediaterelease
(IR) or extended-release (ER) tablet given twice daily to steady state in healthy subjects.
EC 50
for diastolic pressure decrease is 8 ± 5 nM in patients with hypertension.
Reference: Dunselman PH, et al. Felodipine clinical pharmacokinetics. Clin Pharmacokinet,
1991, 21:418–430.
d
CL/F and V/F reported. e Following a 300-mg IR fenofibrate tablet given once daily to steady
state. f Following a 200-mg Mic capsule given once daily to steady state.
References: Balfour JA, et al. Fenofibrate. A review of its pharmacodynamic and pharmacokinetic
properties and therapeutic use in dyslipidaemia. Drugs, 1990, 40:260–290. Miller DB, et al. Clinical
pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet, 1998, 34:155–162.
— b 12 60-70 9.4 ± 4.2 c — 14 ± 6 c 1.3 ± 0.6 e 286 ± 143 ng/mL e
a
Data from healthy adult male subjects. b Absolute bioavailability is unknown. Negligible
metabolism with 85% of a dose recovered in feces unchanged; a substrate for hepatic and
intestinal uptake and efflux transporters. c CL/F and t 1/2
reported for oral dose. d Mild renal
impairment. e Following a 60-mg oral dose twice a day to steady state.
References: Olkkola KT, et al. Clinical pharmacokinetics and pharmacodynamics of opioid
analgesics in infants and children. Clin Pharmacokinet, 1995, 28:385–404.
PDR54, 2000, pp. 405, 1445.
a RD d
i LD
References: Markham A, et al. Fexofenadine. Drugs, 1998, 55:269–274; discussion 275–276.
Robbins OK, et al. Dose proportionality and comparison of single and multiple dose pharmacokinetics
of fexofenadine (MDL 16455) and its enantiomers in healthy male volunteers.
Biopharm Drug Dispos, 1998, 19:455–463.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
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