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

Diazepam a
PO: 100 ± 14 <1 98.7 ± 0.2 0.38 ± 0.06 a 1.1 ± 0.3 43 ± 13 a PO: 1.3 ± IV: 400-500
0.2 b ng/mL b
Rectal: 90 b RD, LD, a Alb a LD, Aged, a Aged, LD Rectal: 1.5 b PO: 317 ± 27
NS, Preg, Neo, Alb ng/mL b
Alb, Burn, Aged
Rectal:
i HTh b LD i RD, HTh i HTh ~400 ng/mL b
i Aged, Smk,
HTh
a
Active metabolites, desmethyldiazepam and oxazepam, formed by CYP2C19 (polymorphic) and
CYP3A. b Range of data following a single 5- to 10-mg IV dose (15- to 30-second bolus) or mean
data following a single 10-mg oral or 15-mg rectal dose given to healthy adults. A concentration
of 300-400 ng/mL provides an anxiolytic effect, and >600 ng/mL provides control of seizures.
Diclofenac
54 ± 2 <1 >99.5 4.2 ± 0.9 a 0.17 ± 0.11 b 1.1 ± 0.2 EC: 2.5 EC: 2.0 (1.4-
(1.0-4.5) c 3.0) μg/mL c
b Aged a RA i RA
i RD, LD, RA SR: 5.3 ± 1.5 c SR: 0.42 ± 0.17
μg/mL c
a
Cleared primarily by CYP2C9-catalyzed 4′-hydroxylation; urine and biliary metabolites
account for 30% and 10-20% of dose, respectively. b V area
reported. c Following a single 50-mg
enteric-coated tablet (EC) or 100-mg sustained-release tablet (SR) given to healthy adults.
Digoxin
References: Friedman H, et al. Pharmacokinetics and pharmacodynamics of oral diazepam:
Effect of dose, plasma concentration, and time. Clin Pharmacol Ther, 1992, 52:139–150.
Greenblatt DJ, et al. Diazepam disposition determinants. Clin Pharmacol Ther, 1980,
27:301–312. PDR54, 2000, p. 1012.
References: Tracy T. Nonsteroidal antiinflammatory drugs. In: Levy RH, et al., eds. Metabolic
Drug Interactions. Philadelphia, Lippincott Williams & Wilkins, 2000, pp. 457–468. Willis
JV, et al. The pharmacokinetics of diclofenac sodium following intravenous and oral administration.
Eur J Clin Pharmacol, 1979, 16:405–410.
70 ± 13 a,c 60 ± 11 25 ± 5 CL = 0.88CL cr
+ V = 3.12CL cr
+ 39 ± 13 l-3 d NT: 1.4 ± 0.7 ng/mL d
0.33 b,c 3.84
i RD, MI, CHF, b RD b LTh b LTh b HTh T: 3.7 ± 1.0 ng/mL d
LTh, HTh, Aged
a HTh, Neo, a HTh a RD, CHF,
Child, Preg
Aged, LTh
i CHF
i Obes
a LANOXIN tablets; digoxin solutions, elixirs, and capsules may be absorbed more completely.
b
Equation applies to patients with some degree of heart failure. If heart failure is not present,
the coefficient of CL cr
is 1.0. Units of CL cr
must be mL/min/kg. c ln the occasional patient,
digoxin is metabolized to an inactive metabolite, dihydrodigoxin, by gut flora. This results in
a reduced oral bioavailability. d Following an oral dose of 0.31 ± 0.19 mg/day or 0.36 ±
0.19 mg/day in patients with CHF who exhibited no signs of digitalis toxicity (NT) or signs of
toxicity (T), respectively. Concentrations >0.8 ng/mL are associated with an inotropic effect.
Concentrations of 1.7, 2.5, and 3.3 ng/mL are associated with a 10%, 50%, and 90% probability
of digoxin-induced arrhythmias, respectively.
References: Mooradian AD. Digitalis. An update of clinical pharmacokinetics, therapeutic monitoring
techniques and treatment recommendations. Clin Pharmacokinet, 1988, 15:165–179.
Smith TW, et al. Digoxin intoxication: The relationship of clinical presentation to serum
digoxin concentration. J Clin Invest, 1970, 49:2377–2386.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1921