Differential effects of flurbiprofen and aspirin on acetazolamide disposition in humans.
The plasma concentration-time profile of acetazolamide (AZ) following an intravenous bolus dose (5 mg kg-1) was determined during control, aspirin and flurbiprofen (FLU) treatment periods. The unbound fraction of AZ in plasma increased three-fold in the presence of salicylate (SA) while, in contrast, FLU produced consistent, but statistically insignificant, increases in binding. SA caused a two-fold decrease in both unbound AZ renal clearance and apparent volume of distribution at steady-state, while FLU produced a small, but significant, increase only in the latter. The area under the concentration-time curve for AZ in erythrocytes was increased by about 40% during SA treatment while FLU had no effect. Our results suggest that on a pharmacokinetic basis FLU may be a safer nonsteroidal anti-inflammatory drug (NSAID) to co-administer with AZ.
Sweeney
K R
KR
School of Pharmacy, University of Connecticut, Storrs 06268.
Chapron
D J
DJ
Antal
E J
EJ
Kramer
P A
PA
D000086:Acetazolamide / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D001241:Aspirin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D005480:Flurbiprofen / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011422:Propionates / Q000494:pharmacology*
D011422:Propionates; D005480:Flurbiprofen; D000086:Acetazolamide; D001241:Aspirin