DESCRIPTION
FIELD OF THE INVENTION
The present invention is related to a Injectable pharmaceutical formulation comprising Amikacin and N-Acetyl cysteine, having lesser side effects. The combination is having less nephrotoxic effects and ototoxic effects as compared to the normal Amikacin injection.
BACKGROUND OF THE INVENTION
JP 2289522 (A) is directed to the use of selected organic acid polymer protectants to inhibit the nephrotoxicity associated with the use of antibiotic aminoglycosides. The invention also covers pharmaceutical compositions comprising such protectants and aminoglycosides for clinical use when coadministration is desired.
JP 2003261459 (A) relates to nephrotoxicity inhibitor of the aminoglucoside-based antibiotics containing a megalin (LRP-2)-binding substance consisting at least one of lysozyme, aprotinin, cytochrome C, a partial peptide of the cytochrome C and a partial peptide of N-WASP of megalin (LRP-2) substrates, and the antibacterial preparation consists of the nephrotoxicity inhibitor having the nephrotoxicity-inhibiting activity and the aminoglucoside-based antibiotic material. Especially, the aminoglucoside-based antibiotic material consists preferably of at least one of gentamicin, amikacin, kanamycin, streptomycin, tobramycin, arbekacin, isepamicin and netilmicin.
JP 4282315 (A) discloses aminoglycoside composition comprising a compound of formula I to formula II (R1 and R2 are each a 2-6C alkyl, cyclohexyl, alkoxyalkyl or hydroxyalkyl; A is a <=4C hydrocarbon group substitutable with methyl; at least one of R3 and R4 is a group of formula III and the other is H or a <=6C aliphatic hydrocarbon group which is interrupted with an oxygen atom having <= two carbon chains or is substitutable with one oxygen atom or two hydroxyl groups; R6 is a 1-3C alkyl; ; (n) is an integer of 2-5), preferably one or more compounds selected from 1,3-di-n-butyl-7-(2-oxopropyl)xanthine and 7-(3-oxobutyl)-1,3-di-n-butylxanthine and is capable of reducing nephrotoxicity of an aminoglycoside such as gentamicin, amikacin, kanamycin and neomycin, especially neomycin.

Amikacin is a commonly used antibacterial drug that can cause significant nephrotoxic effects in both humans and experimental animals. It has been reported that one mechanism of the toxic effects of aminoglycoside antibiotics are the result of oxidative reactions. The aim of this study is to examine the effects of N-acetylcysteine, a thiol-containing antioxidant, on renal function (serum creatinine) and morphology (renal tubular damage) in mice subjected to amikacin-induced nephrotoxicity. A total of 32 mice were equally divided into four groups that were injected with either saline, amikacin (1.2g/kg intraperitoneally), N-acetylcysteine (150mg/kg intraperitoneally for three days) plus amikacin (1.2 g/kg intraperitoneally on the third day as a single dose), or N-acetylcysteine (150mg/kg intraperitoneally). Amikacin administration led to granulovacuolar tubular degeneration in light microscopic examination and myeloid bodies, mitochondrial electron-dense material deposition, and mitochondrial swelling in the proximal tubule epithelium in the electron microscopic evaluation. N-acetylcysteine administration before amikacin injection caused significant decreases in myeloid body and mitochondrial swelling and granulovacuolar tubular degeneration formation. Serum creatinine levels did not change as a result of any treatment. The results show that N-acetylcysteine has a protective effect on nephrotoxicity induced by amikacin. Higher doses of amikacin should be tried to observe biochemical effects.
(Reference-Amikacin-induced nephropathy : Is there any protective way? Author(s) KAYNAR Kubra (1) ; GUL Semih (1) ; ERSOZ Safak (2) ; OZDEMIR Feyyaz (3) ; ULUSOY Hulya (4) ; ULUSOY Sukru (1) ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s) (1) Department of Nephrology, School of Medicine, Karadeniz Technical University, TURQUIE (2) Department of Pathology, School of Medicine, Karadeniz Technical University Feyyaz Ozdemir, TURQUIE(3) Department of Medical Oncology, School of Medicine, Karadeniz Technical University, TURQUIE(4) Department of Anesthesiology, School of Medicine, Karadeniz Technical University, TURQUIE).
Peritonitis is currently one of the leading complications of continuous ambulatory peritoneal dialysis (CAPD). Aminoglycosides and vancomycin are used in the treatment of CAPD peritonitis despite their potential risk for ototoxicity. NAC is a molecule used in the treatment and profilaxy of many diseases related to oxidative stress. The aim of this study was to examine whether ototoxicity due to antibiotics used in the treatment of CAPD peritonitis can be prevented by N-acetylcysteine. (Reference- clinicaltrials.gov) Prevention of aminoglycoside-induced ototoxicity with N-acetylcysteine (reference-
Feldman L et al. Gentamicin-induced ototoxicity in hemodialysis patients is ameliorated by N-

CLAIMS
1. A pharmaceutical formulation comprising Amikacin, and N-Acetyl
cysteine , with the pharmaceutically acceptable excipients.
2. Amikacin, as claimed in claim 1, is present in the range from 75 mg to
600 mg, preferably 100 mg to 500 mg.
3. N-acetyl cysteine, as claimed in claim 1, is present in the range of 200
mg to 600 mg.
4. The pharmaceutical formulation, as claimed in claim 1, is preferably injectable formulation.