Pharmacokinetic-pharmacodynamic relationships of bromfenac in mice and humans.
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 EC50 (the effect site concentration giving 50% of the maximum effect) was estimated to be 0.36 microgram/ml in patients when all five dose groups were combined, and an Emax model was used for pharmacodynamic response. A similar EC50 value, 0.40 microgram/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 EC50 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.
Chiang
S T
ST
Wyeth-Ayerst Research, Princeton, New Jersey, USA.
Ermer
J C
JC
Osman
M
M
Chau
T
T
Hicks
D
D
Wheeler
S
S
Vavra
I
I
D000328:Adult; D000700:Analgesics / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D001577:Benzophenones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D001969:Bromobenzenes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008954:Models, Biological; D010146:Pain / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies
D000700:Analgesics; D001577:Benzophenones; D001969:Bromobenzenes; C053083:bromfenac