Local tissue tolerability of meloxicam, a new NSAID: indications for parenteral, dermal and mucosal administration.
Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which has potent anti-arthritic activity and a reduced potential to induce gastric irritation in animals. The present series of animal studies investigated the local and/or systemic tolerance of meloxicam formulations: intravenous, intramuscular and subcutaneous injections, eye-drops, gel and suppositories. The concentration and formulations were as intended for therapeutic use in man. An in vitro haemolysis test demonstrated that the parenteral formulation of meloxicam produced only minimal haemolysis. In comparison, NSAIDs such as piroxicam, ketoprofen and indomethacin showed comparable haemolysis only after dilution. Diclofenac and ibuprofen caused considerable haemolysis even when diluted. In all studies, the local tolerance of meloxicam was good and did not differ from placebo, even when administered daily for 4 weeks. Few abnormal histopathological findings indicative or organ toxicity were observed. There were only small, transient macroscopic changes at the site of administration, with no striking histopathological changes directly attributable to meloxicam. Intramuscular piroxicam and diclofenac, however, resulted in development of an extensive, solitary necrotic area. Other formulations tested were also very well tolerated. In conclusion, all meloxicam formulations tested exhibited excellent tissue tolerability. Therefore, meloxicam appears to be suitable for parenteral, dermal and mucosal administration.
Stei
P
P
Department of Experimental Pathology and Toxicology, Dr Karl Thomae GmbH, Biberach/Riss, Germany
Kruss
B
B
Wiegleb
J
J
Trach
V
V
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D004361:Drug Tolerance; D005260:Female; D005782:Gels; D006168:Guinea Pigs; D006461:Hemolysis; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D000077239:Meloxicam; D009883:Ophthalmic Solutions; D011817:Rabbits; D051381:Rats; D013488:Suppositories; D013843:Thiazines / Q000008:administration & dosage* / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D009883:Ophthalmic Solutions; D013488:Suppositories; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam