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Pharmacokinetic and Pharmacodynamic Action of Etodolac in Patients after Oral Surgery
Author(s) -
Boni Joseph,
KorthBradley Joan,
McGoldrick Karen,
Appel Alan,
Cooper Stephen
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912709922008254
Subject(s) - etodolac , pharmacodynamics , pharmacokinetics , volume of distribution , medicine , nonmem , placebo , population , anesthesia , pharmacology , alternative medicine , environmental health , pathology
The objective of this double‐blind, randomized, parallel‐group study was to evaluate the pharmacokinetics of etodolac and the pharmacodynamic response of pain in patients following oral surgery who had received 200 or 400 mg of etodolac immediate release (IR), 400 or 1200 mg of etodolac extended release (ER), or a placebo. Etodolac concentrations in 441 plasma samples from 187 patients were analyzed for population pharmacokinetics using the NONMEM program. A one‐compartment pharmacokinetic model with first‐order absorption described the observed data. For etodolac IR, the population mean (%CV) estimates were 3.01 L/h (5.3%) for clearance, 13.6 L (6.8%) for volume of distribution, and 2.31 h −1 (33%) for k a . Respective values for etodolac ER were 3.68 L/h (11%) for clearance, 24.3 L (22%) for volume of distribution, and 0.172 h −1 (24%) for k a . These values generally agreed with previously reported values in healthy adults. Pharmacodynamic assessments included collection of a four‐level categorical rating of pain intensity for up to 24 hours after treatment. Pain intensity difference scores were temporally related to etodolac concentrations and were described using an indirect response model. Mean (%CV) pharmacodynamic parameters were IC 50 of 14.0 mg/L (9.5%), k out of 1.62 h −1 (13%), FR of 0.56 (8.2%), and Hill coefficients that ranged from 1.26 to 3.34 units. A single 1200 mg dose of etodolac ER given once daily was shown to provide substantial efficacy for 13 hours after dose, modest effect through 24 hours, and a more sustained duration of action than the IR dosage form.