Adjuvant arthritis-induced changes on ampicillin binding in serum and tissues under the influence of non-steroidal anti-inflammatory drugs in rats.
Adjuvant arthritis, as a model for investigating rheumatoid arthritis (RA), is characterized by reduced plasma albumin levels and interferes with drug binding in the plasma and tissues (liver and bone). Ampicillin interacts with non-steroidal anti-inflammatory drugs (NSAIDs) due to the acidic pk(a). The aim of this study was to investigate in vitro the concentrations of ampicillin in the serum, femur, mandible and liver proteins following the co-administration of ketoprofen, flurbiprofen, ibuprofen, oxyphenbutazone and ASA in adjuvant arthritis versus healthy control rats. Ampicillin binding was found to be reduced in the serum of arthritic rats, and ampicillin binding to serum proteins was also reduced under the influence of NSAIDs in the control animals. Differences in ampicillin binding were observed in the various tissues due to the effect of adjuvant arthritis as well as that due to the co-administration of NSAIDs. In conclusion, this in vitro study may provide a plausible explanation for the ampicillin-NSAIDs interaction and such a finding may be of therapeutic significance in the treatment of painful arthritic disease such as RA.
Tigka
E
E
Department of Pharmacology, Medical School, University of Athens, Athens, Greece.
Daskala
I
I
Rallis
G
G
Anagnostopoulou
S
S
Tesseromatis
C
C
D000667:Ampicillin / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001169:Arthritis, Experimental / Q000097:blood* / Q000378:metabolism; D001667:Binding, Competitive; D004347:Drug Interactions; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D012709:Serum Albumin; D000667:Ampicillin