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.

The potency of interferon-alpha 2 and interferon-gamma in a combination therapy of dendritic keratitis. A controlled clinical study.

Forty-five patients with virologically confirmed dendritic keratitis were treated in a randomized, double-blind controlled study with a basic therapy of trifluorothymidine (TFT) eye drops. In addition they received different human recombinant interferon (rHu IFN) eye drops. The following results were obtained for average healing times: TFT plus one drop daily of rHu IFN-alpha 2 arg (30 million iu/ml): 3.3 days, TFT plus rHu IFN-gamma (30 million iu/ml): 3.9 days, TFT plus a mixture of alpha plus gamma (0.3 million iu/ml each): 6.1 days, TFT plus a mixture of alpha plus gamma (1.5 million iu/ml each): 3.3 days. High-titer gamma interferon did not significantly differ from high-titer alpha interferon in the combination therapy of dendritic keratitis. A mixture of alpha plus gamma at a moderate titer (1.5 million iu/ml each) was as effective as a high-titer mono-preparation. Adding a low-titer interferon mixture gave no better therapeutic results than antiviral monotherapy. Thus it seems possible to save about 90% of interferon commonly used in the combination therapy of dendritic keratitis by applying a mixture of different suitable interferons instead of interferon monospecies.

[Animal experimental testing of injection solutions for intra-arterial tolerability]. / Zur tierexperimentellen Prüfung von Injektionslösungen auf intraarterielle Verträglichkeit.

Severe damage, even necrosis, has been noted in the past in man after accidental intra-arterial (i.a.) application of injectable preparations intended for intravenous (i.v.) or other parenteral administration. Various experimental models in animals have been developed to test an eventual i.a. incompatibility. Reasons are given for the methodology used by us in the central artery of the rabbit's ear with and without occlusion (harder and softer test variant). Herewith preparations of acetamidoeugenol and thiopental were tested to work out an appropriate measure. In comparison we investigated a series of "placebo solutions" with solvents or other excipients used in the formulation of injection solutions. The "placebos" investigated were then classified with regard to their i.a. compatibility, because in many cases an intra-arterial intolerance can be attributed to them as much as to the active principle. The choice of experimental animal model, the transferability of results to man as well as possible mechanisms taking place in an accidental i.a. application and in the development of ensuing damage are discussed.