RESERVED FOR VETERINARY SURGEONS - 06/2005

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ANIMAL HEALTH YOUR HEALTH RESERVED FOR VETERINARY SURGEONS - 06/2005 LTH AANIMAL HEALTH YOUR HE FATRO - Pharmaceutical Veterinary Industry 40064 Ozzano Emilia (Bo) Italy Tel. +39 051 6512711 - Fax +39 051 6512728 www.fatro.com - e-mail: fatro@fatro.it

+ SPECTINOMYCIN ASSOCIATION LACTIVE SUBSTANCES INCOMYCIN is an antibiotic belonging to the lincosamide class, with characteristics similar to the macrolides. Its spectrum of action includes principally Gram+ bacteria and SPECTINOMYCIN mycoplasmas. SPECTINOMYCIN belongs to the class of the aminocyclitol antibiotics, similar to the aminoglycosides. It is particularly active against Gram- bacteria and mycoplasmas, but also against some Gram+ bacteria. The Lincomycin + Spectinomycin association, in addition to the complementary spectra of antibacterial activity of the two antibiotics, permits a potentiation of the pharmacological action and an anti-bacterial activity which is noticeably greater than when the two antibiotics are used alone. Mycoplasma hyopneumoniae Mycoplasma hyosinoviae Mycoplasma bovirhinis Mycoplasma bovigenitalium Mycoplasma agalactiae Mycoplasma gallisepticum Mycoplasma meleagridis Mycoplasma synoviae Stafilococchi Streptococchi Corinebatteri Bacilli Clostridi Mycoplasmahyorhinis Mycoplasma laidlawii Bordetelle Treponemi Mycoplasma spumans Mycoplasma mycoides Leptospire Mycoplasma maculosum Brucelle Campylobacter spp. Pseudomonas Coliformi Klebsielle MICOSPECTONE Aerobacter Proteus spp. Salmonelle Pasteurelle Emofili ANTIBACTERIAL SPECTRUM OF MICOSPECTONE The figure illustrates the complementary activities and the synergy of action of the Lincomycin + Spectinomycin association. The blue sector shows the microorganisms against which Lincomycin is active, the yellow sector those against which Spectinomycin is efficacious, while the green sector indicates the microorganisms inhibited by the synergic action of both antibiotics. SPECTINOMYCIN

+ SPECTINOMYCIN ASSOCIATION Ribosome Subunit 50S Aminoacyl - t RNA Peptide - t RNA Lincomycin Spectinomycin t RNA P A Subunit 30S THE MECHANISM OF ACTION The synergism of the association is due to the complementary mechanism of action: both antibiotics act by inhibiting protein synthesis; Lincomycin blocks ribosomal subunits 50S, preventing the formation of the peptide bond between the various aminoacids; Spectinomycin bloks subunit 30S and prevents the exact incorporation of the amino acids in the polypeptide chain wich is forming. The antibiotic activity of MICOSPECTONE is potentiated by an alkaline environment and by the presence of serum or whole blood, permitting an intense and efficacious action at the foci of phlogosis, even in the presence of exudates. Central phases of protein synthesis and the block effected by MICOSPECTONE m RNA

Concentration in µg/ml Concentration in µg/ml + SPECTINOMYCIN ASSOCIATION PHARMACOKINETICS After intramuscular administration, the two antibiotics are readily and rapidly absorbed, while after oral administration, action is principally at the gastroenteric level. SPECTINO MYCIN The low degree of drug-protein binding permits a rapid, massive distribution to the various organic systems, also favoured by the low molecular weight of the two active substances. In particular, while Lincomycin, in virtue of its elevated lipophilia, tends to concentrate more in the various tissues of the organism, including bone, Spectinomycin distributes principally to the vascular and extravascular regions. Elevated concentrations are also reached in milk, particularly if the milk tends to be on the alkaline side, as happens in cases of mastitis. Elimination of Lincomycin, after hepatic inactivation, takes place predominantly by the hepatobiliary route, where it reaches concentrations 5-10 times greater than in the serum; Spectinomycin, on the other hand, is eliminated for the most part in unmodified form, via the urine. LOCAL AND GENERAL TOLERANCE The association is characterised by an excellent local and general tolerance, even after repeated administrations. Studies carried out on laboratory animals have demonstrated that the two active substances are not teratogenic and do not have any negative effect on fertility. WITHDRAWAL TIME Milk: 2 days Meat: bovine - swine - ovine 14 days birds 7 days COMPARISION BETWEEN CONCENTRATIONS OF AND SPECTINOMYCIN IN MASTITIC MILK AND IN SERUM OF THE EWE AND THE COW (from Ziv e Sulman, 1973 20 18 16 14 12 10 8 6 4 2 SERUM EWE* 0 0 h 1 h 2 h 3 h 4 h 5 h 6 h 7 h 8 h 9 h 10 h 11 h 12 h 60 50 40 30 20 10 SPECTINOMYCIN SERUM MILK COW* 0 0 h 1 h 2 h 3 h 4 h 5 h 6 h 7 h 8 h 9 h 10 h 11 h 12 h MILK * The animals were treated with the two drugs by the intramuscular route, each at a dose of 20 mg/kg b.w.

+ SPECTINOMYCIN ASSOCIATION MICOSPECTONE IN GENITAL AND MAMMARY DISORDERS In clinical practice with acute forms of mastits and metritis, local treatment alone often fails to reach all of the areas interested by the inflammatory process, and is not sufficient to combat the symptoms of a general nature in the subject. In these cases, use of a parenteral antibiotic with high distribution is an indispensable support to local therapy. MICOSPECTONE is thus indicated in all cases of: ACUTE MASTITIS AND METRITIS IN BOVINES, OVINES-CAPRINES CONTAGIOUS AGALACTIA IN OVINES-CAPRINES MMA SYNDROME IN SOWS MICOSPECTONE IN RESPIRATORY DISORDERS MICOSPECTONE, in virtue of its elevated activity against respiratory pathogens, is particularly efficacious in treatment and prevention of: BACTERIAL AND/OR MYCOPLASMAL PNEUMONIA IN BOVINES,SWINES, OVINES-CAPRINES ENZOOTIC PNEUMONIA DUE TO Mycoplasma Hyopneumoniae IN SWINE PLEUROPNEUMONIA DUE TO Actinobacillus Pleuropneumoniae IN SWINE MICOSPECTONE IN LOCOMOTOR DISORDERS MICOSPECTONE, owing to its high tropism for bone tissue and serous membranes, and owing to its capacity to act optimally even in the presence of exudates, shows itself to be excellent instrument in systemic therapy of inflammatory articular processes and hoof diseases: ARTHRITIS, SEPTIC ARTHROSYNOVITIS, POLYARTHRITIS IN BOVINES, SWINES, OVINES-CAPRINES POLYARTHRITIS/POLYSEROSITIS DUE TO MYCOPLASMAS IN PIGLETS INTERDIGITAL PHLEGMON IN CATTLE OVINE FOOT ROT MICOSPECTONE IN NEONATAL DISORDERS MICOSPECTONE, owing to its immediate, broad-spectrum action, its excellent local and general tolerance and its simplicity of use, is the drug of preference in the various forms of: SEPTICAEMIA OMPHALITIS PNEUMONIA DIARRHOEA POLYARTHRITIS MICOSPECTONE IN ENTERIC PATHOLOGIES MICOSPECTONE is efficacious in the various forms of bacterial enteritis in neonates and in the post-weaning period in the swine and calf, also due to the establishment of the enterohepatic circulation, which permits a prolonged action in the intestine. MICOSPECTONE also efficaciously combats the symptoms of superficial necrotic enteritis which affects fattening swine. MICOSPECTONE IN CUTANEOUS PATHOLOGIES MICOSPECTONE, thanks to its specific activity against Staphylococci, and its capacity to reach appropriate concentrations even in peripheral zones, is the drug of choice in therapy against cutaneous diseases of a bacterial nature; of these, exudative epidermitis in piglets takes on a particular importance due to its severity an widespread nature. Injectable solution POSOLOGIES CATTLE, SHEEP, GOATS AND SWINE: 1 ml/10 Kg b.w. Powder for oral use CALVES: 6 g/100 Kg b.w. PIGLETS: 0,3 g/10 Kg b.w. WITHDRAWAL PERIODS MILK: 2 DAYS MEAT: 14 DAYS

+ SPECTINOMYCIN ASSOCIATION MICOSPECTONE IN AVIAN PATHOLOGY MICOSPECTONE in powder form, owing to its broad spectrum of action which electively includes mycoplasmas, administered in the drinking water, is an excellent means of treatment and control of the most frequent infectious pathologies of a bacterial nature in Avian species. In particular, MICOSPECTONE possesses a high degree of efficacy against: AVIAN MYCOPLASMAS COLIBACILLOSIS SALMONELLOSIS AVIAN CHOLERA INFECTIOUS CORYZA DUE HAEMOPHILUS SPP. INFECTIONS DUE STAPHYLOCOCCI AND STREPTOCOCCI C.R.D. due to Mycoplasma gallisepticum Synovitis due to Mycoplasma synoviae Infections due Mycoplasma meleagridis Pullorum disease Fowl typhoid Arizona disease Salmonellosis in general powder for oral use POSOLOGIES UP TO 3 WEEKS OF AGE 3 g/10 Kg b.w. M I C O S P E C T O N E Two active substances with a synergic effect in one single intramuscular administration Excellent local and general tolerance even in neonate animals Rapid, elevated absorption of the active substances Maximum distribution with elevated tropism for foci of phlogosis Short withdrawal periods for meat and milk MICOSPECTONE AFTER 3 WEEKS Of AGE 1 g/10 Kg b.w. WITHDRAWAL PERIODS MEAT: 7 DAYS