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Pharmacokinetic‐Pharmacodynamic Relationships of Bromfenac in Mice and Humans
Author(s) -
Chiang Soong T.,
Ermer James C.,
Osman Mohamed,
Chau Thuy,
Hicks David,
Wheeler Sarah,
Vavra Ivan
Publication year - 1996
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1996.tb03048.x
Subject(s) - pharmacodynamics , pharmacokinetics , pharmacology , medicine
The relationship between pharmacodynamic effect and plasma concentrations of the analgesic bromfenac was assessed retrospectively. The drug was administered in single doses of 5, 10, 25, 50, or 100 mg to patients with oral surgery pain. Concentration‐effect curves were generated by a semiparametric pharmacokinetic‐pharmacodynamic procedure. The bromfenac EC 50 (the effect site concentration giving 50% of the maximum effect) was estimated to be 0.36 μg/ml in patients when all five dose groups were combined, and an E max model was used for pharmacodynamic response. A similar EC 50 value, 0.40 μg/ml, was obtained when bromfenac was tested in a mouse pain model. On the basis of combined‐dose data, effect site concentrations were predicted to be above the analgesic EC 50 for approximately 7–8 hours after a 50‐mg bromfenac dose was taken in the fasting state. Predictions based on a pharmacokinetic‐pharmacodynamic modeling procedure were in reasonable agreement with the clinical observations.