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

Nitrofurantoin
87 ± 13 47 ± 13 62 ± 4 9.9 ± 0.9 0.58 ± 0.12 1.0 ± 0.2 2.3 ± 1.4 a 428 ± 146 ng/mL a
a Alkaline urine
i Alkaline urine
a
Following a single 50-mg oral dose (tablet) given to fasted healthy adults. No changes when
taken with a meal.
Nitroglycerin a
PO: <1 <1 — 195 ± 86 c 3.3 ± 1.2 c,d 2.3 ± 0.6 min SL: 0.09 ± IV: 3.4 ± 1.7 ng/mL e
0.03 e
SL: 38 ± 26 b Top: 3-4 e SL: 1.9 ± 1.6 ng/mL e
Top: 72 ± 20
TD: 2 e
a
Dinitrate metabolites have weak activity compared to nitroglycerin (<10%), but because of a
prolonged t 1/2
(~40 min), they may accumulate during administration of sustained-release
preparations to yield concentrations in plasma 10- to 20-fold greater than parent drug.
b
Following sublingual (SL) dose rinsed out of mouth after 8 minutes. Rinse contained 31 ±
19% of the dose. c Following a 40- to 100-minute IV infusion. d V area
reported. e Steady-state
concentration following a 20-54 μg/min IV infusion over 40-100 minutes or a 0.4-mg SL
Nortriptyline a
51 ± 5 2 ± 1 92 ± 2 7.2 ± 1.8 b 18 ± 4 c 31 ± 13 b 7-10 138 (40-350) nM d
a HL b Aged, Inflam a Aged
i Smk, RD
i RD
a
Active metabolite, 10-hydroxynortriptyline, accumulates to twice the concentration of nortriptyline
in extensive metabolizers. Formation of 10-hydroxynortriptyline is catalyzed by
CYP2D6 (polymorphic). b For poor metabolizers, CL/F is lower (5.3 versus 19.3 mL/min/kg)
and t 1/2
longer (54 versus 21 hours) than that of extensive metabolizers. c V area
reported. d Mean
following a 125-mg oral dose given once daily to healthy adults to steady state.
Antidepressant effect observed at levels of 190-570 nM. Appears less effective at plasma
concentrations >570 nM.
Olanzapine a
Reference: Hoener B, et al. Nitrofurantoin disposition. Clin Pharmacol Ther, 1981,
29:808–816.
dose. Levels of 1.2-11 ng/mL associated with a 25% drop in capillary wedge pressure in
patients with CHF. T max
for topical (Top) and transdermal (TD) preparations also reported.
References: Noonan PK, et al. Incomplete and delayed bioavailability of sublingual nitroglycerin.
Am J Cardiol, 1985, 55:184–187. PDR54, 2000, p. 1474. Thadani U, et al. Relationship
of pharmacokinetic and pharmacodynamic properties of the organic nitrates. Clin
Pharmacokinet, 1988, 15:32–43.
~60 b 7.3 93 6.2 ± 2.9 c 16.4 ± 5.1 c 33.1 ± 10.3 6.1 ± 1.9 d 12.9 ± 7.5 ng/mL d
i RD, LD
a Aged
a
Data from male and female schizophrenic patients. Metabolized primarily by UGT,
CYP1A2, and flavin-containing monooxygenase. b Bioavailability estimated from parentmetabolite
recovery data. c Summary of CL/F and V area
/F for 491 subjects receiving an oral
dose. CL/F segregates by sex (F/M) and smoking status (NS/S): M, S > F, S > M, NS > F, NS.
d
Following a single 9.5 ± 4-mg oral dose to healthy male subjects; C max,ss
~20 ng/mL following
a 10-mg oral dose given once daily.
References: Dalen P, et al. 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3,
and 13 functional CYP2D6 genes. Clin Pharmacol Ther, 1998, 63:444–452. Jerling M, et al.
Population pharmacokinetics of nortriptyline during monotherapy and during concomitant
treatment with drugs that inhibit CYP2D6—An evaluation with the nonparametric maximum
likelihood method. Br J Clin Pharmacol, 1994, 38:453–462. Ziegler VE, et al. Nortriptyline
plasma levels and therapeutic response. Clin Pharmacol Ther, 1976, 20:458–463.
References: Callaghan JT, et al. Olanzapine. Pharmacokinetic and pharmacodynamic profile.
Clin Pharmacokinet, 1999, 37:177–193. Kassahun K, et al. Disposition and biotransformation
of the antipsychotic agent olanzapine in humans. Drug Metab Dispos, 1997, 25:81–93.
PDR54, 2000, p. 1649.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1959