| Indication |
For short-term treatment of serious infections due to susceptible
strains of Gram-negative bacteria, including Pseudomonas species,
Escherichia coli, species of indole-positive and indole-negative
Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species,
and Acinetobacter (Mima-Herellea) species. Amikacin may also be used to
treat Mycobacterium avium and Mycobacterium tuberculosis infections. |
| Pharmacodynamics |
Amikacin is an aminoglycoside antibiotic. Aminoglycosides work
by binding to the bacterial 30S ribosomal subunit, causing misreading of
t-RNA, leaving the bacterium unable to synthesize proteins vital to its
growth. Aminoglycosides are useful primarily in infections involving
aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and
Enterobacter. In addition, some mycobacteria, including the bacteria
that cause tuberculosis, are susceptible to aminoglycosides. Infections
caused by Gram-positive bacteria can also be treated with
aminoglycosides, but other types of antibiotics are more potent and less
damaging to the host. In the past the aminoglycosides have been used in
conjunction with penicillin-related antibiotics in streptococcal
infections for their synergistic effects, particularly in endocarditis.
Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi
and viruses. |
| Mechanism of action |
Aminoglycosides like Amikacin "irreversibly" bind to specific
30S-subunit proteins and 16S rRNA. Amikacin inhibits protein synthesis
by binding to the 30S ribosomal subunit to prevent the formation of an
initiation complex with messenger RNA. Specifically Amikacin binds to
four nucleotides of 16S rRNA and a single amino acid of protein S12.
This interferes with decoding site in the vicinity of nucleotide 1400 in
16S rRNA of 30S subunit. This region interacts with the wobble base in
the anticodon of tRNA. This leads to interference with the initiation
complex, misreading of mRNA so incorrect amino acids are inserted into
the polypeptide leading to nonfunctional or toxic peptides and the
breakup of polysomes into nonfunctional monosomes. |
| Absorption |
Rapidly absorbed after intramuscular administration. Rapid
absorption occurs from the peritoneum and pleura. Poor oral and topical
absorption. Poorly absorbed from bladder irrigations and intrathecal
administration. |
| Volume of distribution |
- 24 L [normal adult subjects]
|
| Protein binding |
0-11% |
| Metabolism |
Not Available |
| Route of elimination |
Amikacin is excreted primarily by glomerular filtration. |
| Half life |
2-3 hours |
| Clearance |
|
| Toxicity |
Mild and reversible nephrotoxicity may be observed in 5 - 25% of
patients. Amikacin accumulates in proximal renal tubular cells. Tubular
cell regeneration occurs despite continued drug exposure. Toxicity
usually occurs several days following initiation of therapy.
May cause irreversible ototoxicity. Otoxocity appears to be correlated
to cumulative lifetime exposure. Drug accumulation in the endolymph and
perilymph of the inner ear causes irreversible damage to hair cells of
the cochlea or summit of ampullar cristae in the vestibular complex.
High frequency hearing is lost first with progression leading to loss of
low frequency hearing. Further toxicity may lead to retrograde
degeneration of the 8th cranial (vestibulocochlear) nerve. Vestibular
toxicity may cause vertigo, nausea, vomiting, dizziness and loss of
balance. |
