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

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SECTION IV
Table 34–1
Classification and Comparison of Nonsteroidal Analgesics (Continued)
CLASS/DRUG
(SUBSTITUTION) PHARMACOKINETICS DOSING d COMMENTS COMPARED TO ASPIRIN
Meloxicam Peak C p
5-10 hours 7.5-15 mg/day Some COX-2
Protein binding 99% selectivity, especially
Metabolites Hydroxylation at lower doses
t 1/2
15-20 hours
Nabumetone Peak C p
3-6 hours 500-1000 mg 1-2 times/day A prodrug, rapidly Shows some COX-2
(naphthyl Protein binding 99% metabolized to 6-methoxy- selectivity (active
alkanone) Major metabolites O-demethylation, 2-naphthyl acetic acid; metabolite does not)
then conjugation pharmacokinetics reflect Fewer GI side effects
t 1/2
24 hours active compound than many NSAIDs
Diaryl heterocyclic NSAIDs Evidence for Decrease in GI side
(COX-2 selective) cardiovascular effects and in
adverse events
platelet effects
Celecoxib Peak C p
2-4 hours 100 mg 1-2 times/day Substrate for CYP2C9; See the text for an
[diaryl Protein binding 97% inhibitor of CYP2D6 overview of COX-2
substituted Metabolites Carboxylic acid Coadministration with inhibitors
pyrazone; and glucuronide inhibitors of CYP2C9 or
(sulfonamide conjugates substrates of CYP2D6
derivative)] t 1/2
6-12 hours should be done with
caution
Parecoxib
Etoricoxib Not approved for use in the U.S.
Lumaricoxi
a
Time to peak plasma drug concentration (C p
) after a single dose. In general, food delays absorption but does not decrease peak concentration. b The majority of NSAIDs undergo hepatic metabolism,
and the metabolites are excreted in the urine. Major metabolites or disposal pathways are listed. c Typical t 1/2
is listed for therapeutic doses; if t 1/2
is much different with the toxic dose, this is
also given. d Limited dosing information given. For additional information, refer to the text and product information literature. Additional references can be found in earlier editions of this textbook.
CNS, central nervous system; COX, cyclooxygenase; GI, gastrointestinal; IM, intramuscularly; IV, intravenously.