Clinical response to non-steroidal anti-inflammatory drugs in urate-crystal induced inflammation: a simultaneous study of intersubject and intrasubject variability.
1. It is well known that an individual subject often responds preferentially to a particular nonsteroidal anti-inflammatory drug (NSAID) and clinical response to these drugs is characterised by considerable variability between individuals. Variability in response has often been attributed to the episodic nature of musculoskeletal disease. Few studies have studied intrasubject variability in response to these drugs using a multiple crossover design. A major difficulty has been the lack of objective, validated measures of inflammation sensitive to NSAIDs. The primary aim of the present study was to test the utility of urate-crystal induced inflammation as a tool to predict NSAID response in humans. 2. An inflammatory reaction was established in twenty-five healthy subjects with intradermal injection of urate crystals on four separate occasions separated by 1 week. Each subject was randomly assigned to receive either ibuprofen on two of these occasions (800 mg four times over 36 h) or matched placebo on the other two occasions using a double-blind, cross-over design. Decrease in the area under the wheal size-time curve was used to indicate anti-inflammatory response. 3. Peak inflammatory response was observed at about 32 h and had dissipated by 56 h post-urate injection. The logarithmic mean wheal area was significantly lower after ibuprofen (mean +/- s.e. mean; 6.74 +/- 0.09) compared with placebo (6.96 +/- 0.07 mm h); a difference of 20% (95% confidence interval for difference: 1 to 35%; P < 0.05). 4. There was marked intra- and intersubject variability in response to ibuprofen over the four treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)
Walker
J S
JS
Department of Clinical Pharmacology, St Vincent's Hospital, Sydney, NSW, Australia.
Nguyen
T V
TV
Day
R O
RO
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D003198:Computer Simulation; D018592:Cross-Over Studies; D003460:Crystallization; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D014527:Uric Acid / Q000008:administration & dosage / Q000009:adverse effects*
D014527:Uric Acid; D007052:Ibuprofen