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

5-Fluorouracil (5-FU)
28 (0-80) a <10 8-12 16 ± 7 0.25 ± 0.12 11 ± 4 min b — 11.2 μM c
a
Higher F with rapid absorption and lower F with slower absorption, due to a saturable firstpass
effect. b A much longer (~20 hours) terminal t 1/2
has been reported, representing a slow
redistribution of drug from tissues. c Steady-state concentration following a continuous IV
infusion of 300-500 mg/m 2 /day to cancer patients.
Fluoxetine a
— a <2.5 94 9.6 ± 6.9 b,c 35 ± 21 d 53 ± 41 e F: 6-8 f F: 200-531 ng/mL f
i LD, RD i RD, Aged, Obes i RD, LD a LD NF: 103-465 ng/mL f
b LD
i RD, Aged,
Obes
a
Active metabolite, norfluoxetine; t 1/2
of norfluoxetine is 6.4 ± 2.5 days (12 ± 2 days in cirrhosis).
Absolute bioavailability is unknown, but ≥80% of the dose is absorbed. b Reduced CL
with repetitive dosing (~2.6 mL/min/kg) and with increasing dose between 40 and 80 mg.
c
CL/F reported; fluoxetine is a CYP2D6 substrate and inhibitor. d V area
/F reported. e Longer t 1/2
with repetitive dosing and with increasing doses. f Range of data for fluoxetine (F) and
Fluphenazine a
PO: 2.7 (1.7-4.5) b Negligible — 10 ± 7 11 ± 10 IV: 12 ± 4 c IR: 2.8 ± 2.1 d IR: 2.3 ± 2.1 ng/mL d
SC or IM: IR: 14.4 ± 7.8 c DN: 24-48 d DN: 1.3 ng/mL d
3.4 (2.5-5.0) b SR: 20.3 ± 7.9 c EN: 48-72 d EN: 1.1 ng/mL d
a
Data from healthy male and female volunteers. Fluphenazine is extensively metabolized.
b
Available in immediate-release (IR) oral and IM formulations and depot SC or IM injections as
the enanthate (EN) or decanoate (DN) esters. Geometric mean (90% confidence interval).
c
Reported t 1/2
for a single IV dose and apparent t 1/2
following oral administration of IR and slowrelease
(SR) formulations. Longer apparent t 1/2
s with oral dosing reflect an absorption-limited
elimination. d Following a single 12-mg oral dose (IR) or 5-mg IM injections of DN and EN.
Flutamide a
Reference: Diasio RB, et al. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet,
1989, 16:215–237.
norfluoxetine (NF) following a 60-mg oral dose given once daily for 1 week. NF continues to
accumulate for several weeks.
Reference: Altamura AC, et al. Clinical pharmacokinetics of fluoxetine. Clin Pharmacokinet,
1994, 26:201–214.
— <1 F: 94-96 280 b — F: 7.8 b F: 1.3 ± 0.7 c F: 0.11 ± 0.21 μg/mL c
HF: 92-94 i RD HF: 8.1 b HF: 1.9 ± 0.6 c HF: 1.6 ± 0.59 μg/mL c
a
Data obtained primarily from elderly men. Flutamide (F) is metabolized rapidly to a number
of metabolites, which are mainly excreted in urine. One major metabolite, 2-hydroxyflutamide
(HF), is biologically active (equal potency); formation is catalyzed primarily by
CYP1A2. b CL/F and t 1/2
(terminal) reported for oral dose. c Data for F and HF following a
250-mg oral dose given three times daily to steady state in healthy geriatric male volunteers.
References: Jann MW, et al. Clinical pharmacokinetics of the depot antipsychotics. Clin
Pharmacokinet, 1985, 10:315–333. Koytchev R, et al. Absolute bioavailability of oral immediate
and slow release fluphenazine in healthy volunteers. Eur J Clin Pharmacol, 1996,
51:183–187.
References: Anjum S, et al. Pharmacokinetics of flutamide in patients with renal insufficiency.
Br J Clin Pharmacol, 1999, 47:43–47. PDR54, 2000, p. 2798. Radwanski E, et al. Single and
multiple dose pharmacokinetic evaluation of flutamide in normal geriatric volunteers. J Clin
Pharmacol, 1989, 29:554–558.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1933