AMIKACIN

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.
The bioavailability of this drug is expected to vary primarily from individual differences in nebulizer efficiency and airway pathology.
Following IM administration of a single dose of amikacin of 7.5 mg/kg in adults with normal renal function, peak plasma amikacin concentrations of 17-25 micrograms/mL are attained within 45 minutes to 2 hours.
Following IV infusion of the same dose given over 1 hour peak plasma concentrations of the drug average 38 micrograms/mL immediately following the infusion, 5.5 micrograms/mL at 4 hours, and 1.3 micrograms/mL at 8 hours.

Toxicity

Oral (LD50): 6000 mg/kg (Mouse) . No antidote for toxicity is currently available. This drug is only 20% dialyzable; however, this is variable based on the type hemodialysis filter used.
Nephrotoxicity
Mild and reversible nephrotoxicity may be observed in 5 - 25% of patients. Amikacin accumulates in the proximal renal tubular cells. Tubular cell regeneration occurs despite continued drug exposure. Toxicity most commonly occurs several days following initiation of therapy. Amikacin may exacerbate pre-existing renal disease.
Ototoxicity
May cause irreversible ototoxicity. Ototoxicity appears to be correlated to cumulative 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.
Neuromuscular blockade
In addition to the above, amikacin may exacerbate neuromuscular blockade, however, this is less common.
Use in Pregnancy
Category D. Gentamicin and other aminoglycosides are known to cross the placenta. There is evidence of selective uptake of gentamicin by the fetal kidney resulting in damage to immature nephrons. Eighth cranial nerve damage has also been reported after in-utero exposure to some of the aminoglycosides. Because of the chemical similarity, all aminoglycosides should be considered potentially nephrotoxic and ototoxic to the developing fetus. Therapeutic blood amikacin levels in the mother do not equate with safety for the fetus. In reproductive toxicity studies in mice and rats, no effects on fertility or fetal toxicity were observed.
Use in Lactation
It is not known whether amikacin is excreted in breast milk. Since the possible harmful effect on the infant is not known, it is recommended that if nursing mothers must be given amikacin, the infants should not be breastfed during therapy.

Description

Amikacin is made semisynthetically from kanamycin A. Interestingly, the L-hydroxyaminobutyryl amide (HABA) moiety attached to N-3 inhibits adenylation and phosphorylation in the distant amino sugar ring (at C-2′and C-3′), even though the HABA substituent is not where the enzymatic reaction takes place. This effect is attributed to decreased binding to the R factor–mediated enzymes.

Chemical properties

white crystalline powder

Originator

Amikin,Bristol,US,1976

The Uses of AMIKACIN

Amikacin is a semi-synthetic derivative of kanamycin. It is much less sensitive to the enzymes that inactivate aminoglycoside antibiotics. The spectrum is similar to that of gentamicin. Amikacin principally finds use in the treatment of infections arising from bacteria that are resistant to gentamicin and/or tobramycin.

The Uses of AMIKACIN

Antibacterial;Ribosomal protein synthesis inhibitor

The Uses of AMIKACIN

Amikacin is highly effective with respect to Gram-negative microorganisms (blue-pus and gastric bacilli, rabbit fever, serratia, providencia, enterobacteria, proteus, salmonella, shigella), as well as Gram-positive microorganisms (staphylococci, including those that are resistant to penicillin and some cephalosporins), and a few strains of streptococci.
It is used for severe bacterial infections: peritonitis, sepsis, meningitis, osteomyelitis, endocarditis, pneumonia, pleural empyema, pulmonary abscess, purulent skin and soft tissue infections, and infections of the urinary tract that are caused by microorganisms sensitive to the drug. Synonyms of this drug are amikin, biklin, novamin, and others.

What are the applications of Application

Amikacin (free base) is an aminoglycoside antibiotic derived from kanamycin A

Indications

The amikacin sulfate injection is indicated in the short-term treatment of serious bacterial 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, as well as Acinetobacter (Mima-Herellea) species.
Clinical studies have shown amikacin sulfate injection to be effective in bacterial septicemia (including neonatal sepsis); in serious infections of the respiratory tract, bones and joints, central nervous system (including meningitis) and skin and soft tissue; intra-abdominal infections (including peritonitis); and in burns and postoperative infections (including post-vascular surgery).
Clinical studies have shown amikacin also to be effective in serious, complicated, and recurrent urinary tract infections due to the above organisms. Aminoglycosides, including amikacin, are not indicated in uncomplicated first-time episodes of urinary tract infections unless the causative organisms are not susceptible to antibiotics which are less toxic.
In September 2018, a new indication with a new dosage route was approved for this drug. Amikacin liposome inhalation suspension was approved for the treatment of lung disease caused by a group of bacteria, Mycobacterium avium complex (MAC) in a limited population of patients with the disease who do not respond to conventional treatment (refractory disease). This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6 of treatment. Clinical benefit has not yet been established.
Important notes regarding Staphylococcus and Sensitivity testing:
Staphylococcus aureus, including methicillin-resistant strains, is the principal Gram-positive organism sensitive to amikacin. The use of amikacin in the treatment of staphylococcal infections should be restricted only to second-line therapy, and should be limited to only those patients suffering from severe infections caused by susceptible strains of staphylococcus species who have failed to show sensitivity to other available antibiotics.
Bacteriologic studies should be performed to identify causative organisms and their susceptibilities to amikacin. Amikacin may be used as initial therapy in suspected gram-negative infections and therapy may be initiated before obtaining the results of susceptibility testing.

Background

Amikacin is a semi-synthetic aminoglycoside antibiotic that is derived from kanamycin A. Amikacin is synthesized by acylation with the l-(-)-γ-amino-α-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety of kanamycin A.
Amikacin's unique property is that it exerts activity against more resistant gram-negative bacilli such as Acinetobacter baumanii and Pseudomonas aeruginosa. Amikacin also exerts excellent activity against most aerobic gram-negative bacilli from the Enterobacteriaceae family, including Nocardia and some Mycobacterium (M. avium-intracellulare, M. chelonae, and M. fortuitum). M. avium-intracellulare (MAC) is a type of nontuberculous mycobacteria (NTM) found in water and soil. Symptoms of this disease include a persistent cough, fatigue, weight loss, night sweats, and shortness of breath and the coughing up of blood.
Several forms of amikacin are used currently, including an intravenous (IV) or intramuscular (IM) injection. In September 2018, a liposomal inhalation suspension of this drug was approved by the FDA for the treatment of lung disease caused by Mycobacterium avium complex (MAC) bacteria in a small population of patients with the disease who do not respond to traditional treatment.

Definition

ChEBI: An amino cyclitol glycoside that is kanamycin A acylated at the N-1 position by a 4-amino-2-hydroxybutyryl group.

Manufacturing Process

Preparation of L-(-)-γ-benzyloxycarbonylamino-α-hydroxybutyric acid: L-(-)-γ- amino-α-hydroxybutyric acid (7.4 g, 0.062 mol) was added to a solution of 5.2 grams (0.13 mol) of sodium hydroxide in 50 ml of water. To the stirred solution was added dropwise at 0-5°C over a period of 0.5 hour, 11.7 grams (0.068 mol) of carbobenzoxy chloride and the mixture was stirred for another hour at the same temperature. The reaction mixture was washed with 50 ml of ether, adjusted to pH 2 with dilute hydrochloric acid and extracted with four 80 ml portions of ether. The ethereal extracts were combined, washed with a small amount of saturated sodium chloride solution, dried with anhydrous sodium sulfate and filtered. The filtrate was evaporated in vacuum and the resulting residue was crystallized from benzene to give 11.6 grams (74%) of colorless plates; MP 78.5°C to 79.5°C.
Preparation of N-Hydroxysuccinimide Ester of L-(-)-γ-Benzyloxycarbonylamino- α-hydroxybutyric acid: A solution of 10.6 grams (0.042 mol) of L-(-)-γ- benzyloxycarbonylamino-α-hydroxybutyric acid and 4.8 grams (0.042 mol) of N-hydroxysuccinimide in 200 ml of ethyl acetate was cooled to 0°C and then 8.6 grams (0.042 mol) of dicyclohexylcarbodiimide was added. The mixture was kept overnight in a refrigerator. The dicyclohexylurea which separated was filtered off and the filtrate was concentrated to about 50 ml under reduced pressure to give colorless crystals of L-(-)-γ-benzyloxycarbonylamino- α-hydroxybutyric acid which were collected by filtration; 6.4 grams, MP 121- 122.5°C. The filtrate was evaporated to dryness in vacuum and the crystalline residue was washed with 20 ml of a benzene-n-hexane mixture to give an additional amount of L-(-)-γ-benzyloxycarbonylamino-α-hydroxybutyric acid. The total yield was 13.4 grams (92%).
Preparation of 1-[L-(-)-γ-Benzyloxycarbonylamino-α-Hydroxybutyryl]-6'- Carbobenzoxykanamycin A: A solution of 1.6 grams (4.6 mmol) of L-(-)-γ- benzyloxycarbonylamino-α-hydroxybutyric acid in 40 ml of ethylene glycol dimethyl ether (DME) was added dropwise to a stirred solution of 2.6 grams (4.2 mmol) of 6'-monobenzyloxycarbonylkanamycin A in 40 ml of 50% aqueous ethylene glycol dimethyl ether and the mixture was stirred overnight. The reaction mixture was evaporated under reduced pressure to give a brown residue 1-[L-(-)-γ-benzyloxycarbonylarnino-α-hydroxybutyryl]-6'- carbobenzoxykanamycin A which was used for the next reaction without further purification.
Preparation of 1-[L-(-)-γ-Amino-α-Hydroxybutyryl] Kanamycin A: The crude product 1-[L-(-)-γ-benzyloxycarbonylamino-α-hydroxybutyryl]-6'- carbobenzoxykanamycin A was dissolved in 40 ml of 50% aqueous dioxane and a small amount of insoluble material was removed by filtration. To the filtrate was added 0.8 ml of glacial acetic acid and 1 gram of 10% palladiumon- charcoal and the mixture was hydrogenated at room temperature for 24 hours in a Parr hydrogenation apparatus. The reaction mixture was filtered to remove the palladium catalyst and the filtrate was evaporated to dryness in vacuum.
The residue was dissolved in 30 ml of water and chromatographed on a column of CG-50 ion exchange resin (NH4 + type, 50 cm x 1.8 cm). The column was washed with 200 ml of water and then eluted with 800 ml of 0.1 N NH4OH, 500 ml of 0.2 N NH4OH and finally 500 ml of 0.5 N NH4OH. Ten milliliter fractions were collected and fractions 146 to 154 contained 552 mg (22%. based on carbobenzoxykanamycin A, 6'- monobenzyloxycarbonylkanamycin A) of the product which was designated BB-K8 lot 2. MP 187°C (dec). Relative potency against B. subtilis (agar plate) = 560 mcg/mg (standard: kanamycin A free base).
A solution of 250 mg of BB-K8 lot 2 in 10 ml of water was subjected to chromatography on a column of CG-50 (NH4 + type, 30 cm x 0.9 cm). The column was washed with 50 ml of water and then eluted with 0.2 N NH4OH. Ten milliliter fractions were collected. Fractions 50 to 63 were combined and evaporated to dryness under reduced pressure to give 98 mg of the pure product base.
Preparation of the Monosulfate Salt of 1-[L-(-)-γ-Amino-α-Hydroxybutyryl] Kanamycin A: One mol of 1-[L-(-)-γ-amino-α-hydroxybutyryl] kanamycin A is dissolved in 1 to 3 liters of water. The solution is filtered to remove any undissolved solids. To the chilled and stirred solution is added one mol of sulfuric acid dissolved in 500 ml of water. The mixture is allowed to stir for 30 minutes, following which cold ethanol is added to the mixture till precipitation occurs. The solids are collected by filtration and are determined to be the desired monosulfate salt.

brand name

Amikin (Apothecon).

Therapeutic Function

Antibacterial

Antimicrobial activity

Among other organisms, Acinetobacter, Alkaligenes, Campylobacter, Citrobacter, Hafnia, Legionella, Pasteurella, Providencia, Serratia and Yersinia spp. are usually susceptible in vitro. Stenotrophomonas maltophilia, many nonaeruginosa pseudomonads and Flavobacterium spp. are resistant. M. tuberculosis (including most streptomycin-resistant strains) and some other mycobacteria (including M. fortuitum and the M. avium complex) are susceptible; most other mycobacteria, including M. kansasii, are resistant. Nocardia asteroides is susceptible.
It exhibits typical aminoglycoside characteristics, including an effect of divalent cations on its activity against Ps. aeruginosa analogous to that seen with gentamicin and synergy with β-lactam antibiotics.

Acquired resistance

Amikacin is unaffected by many of the modifying enzymes that inactivate gentamicin and tobramycin and is consequently active against staphylococci, enterobacteria and Pseudomonas that owe their resistance to the production of those enzymes. However, AAC(6′), ANT(4′) and some forms of APH(3′) can confer resistance; because these enzymes generally do not confer gentamicin resistance, amikacin-resistant strains can be missed in routine susceptibility tests when gentamicin is used as the representative aminoglycoside.
There have been reports of resistance arising during treatment of infections due to Serratia spp. and Ps. aeruginosa. Outbreaks of infection with multiresistant strains of enterobacteria and Ps. aeruginosa have occurred after extensive use, particularly in burns units. Bacteria that owe their resistance to the expression of ANT(4′) have been described in Staph. aureus, coagulase-negative staphylococci, Esch. coli, Klebsiella spp. and Ps. aeruginosa. In E. faecalis, resistance to penicillin– aminoglycoside synergy has been associated with plasmidmediated APH(3′). Resistance in Gram-negative organisms is usually caused by either reduced accumulation of the drug or, more commonly, by the aminoglycoside-modifying enzymes AAC(6′) or AAC(3)-VI. The latter enzyme is usually found in Acinetobacter spp., but has also been found, encoded by a transposon, in Prov. stuartii. One type of AAC(6) is chromosomally encoded by Ser. marcescens, though not usually expressed.
The prevalence of resistance to amikacin remains low (<5%) in many countries but can change rapidly with increased usage of the drug. However, the spread of extended spectrum β-lactamases belonging to the TEM and SHV families may result in an increase in amikacin resistance that is not associated with use, since most strains that produce such enzymes also produce AAC(6′).

General Description

Amikacin was synthesized by Kawaguchi et al. of the Bristol-Banyu Research Institute in 1970 starting with kanamycin and the acyl moiety of butirosin. Its design is based on knowledge of the mechanisms of bacterial resistance to kanamycin and related compounds in which the 3 -hydroxyl group of the antibiotic is phosphorylated enzymatically. The acyl moiety in butirosin prevents this enzymatic inactivation.

Pharmacokinetics

Amikacin is an aminoglycoside antibiotic. Aminoglycosides bind to the bacteria, causing misreading of t-RNA, leaving bacteria unable to synthesize proteins vital to their growth. Aminoglycosides are useful mainly in the treatment 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, however, other antibiotics may be more potent and less toxic to humans.

Pharmacokinetics

C_{max 7.5 mg/kg intramuscular： c. 30 mg/L after 1 h
500 mg 30-min infusion： 35–50 mg/L end infusion
15 mg/kg 30-min infusion： >50 mg/L after 1 h
Plasma half-life： 2.2 h
Volume of distribution： 0.25–0.3 L/kg
Plasma protein binding： 3–11%
It is readily absorbed after intramuscular administration. Rapid intravenous injection of 7.5 mg/kg produced concentrations in excess of 60 mg/L shortly after injection.
Most pharmacokinetic parameters follow an almost linear correlation when the once-daily doses (15 mg/kg) are compared with the traditional 7.5 mg/kg twice daily. In patients on CAPD, there was no difference in mean peak plasma concentration or volume of distribution whether the drug was given intravenously or intraperitoneally. However, in patients with significant burn injuries, doses should be increased to 20 mg/kg.
In infants receiving 7.5 mg/kg by intravenous injection, peak plasma concentrations were 17–20 mg/L. No accumulation occurred on 12 mg/kg per day for 5–7 days. There was little change in the plasma concentration or the half-life (1.7 and 1.9 h) on the third and seventh days of a period over which 150 mg/m2 was infused over 30 min every 6 h. When the dose was raised to 200 mg/m2 the concentration never fell below 8 mg/L. The plasma half-life was longer in babies of lower birth weight and was still 5–5.5 h in babies aged 1 week or older. The importance of dosage control in the neonate is emphasized by the findings that there is an inverse relationship between post-conception age and plasma elimination half-life, though in extremely premature babies the weight of the child is also a significant predictor of half-life.}

Clinical Use

Severe infection (including septicemia, neonatal sepsis, osteomyelitis, septic arthritis, respiratory tract, urinary tract, intra-abdominal, peritoneal and soft tissue infections) caused by susceptible micro-organisms Sepsis of unknown origin (combined with a β-lactam or anti-anaerobe agent as appropriate).
Mycobacterial infection
Amikacin is principally used for the treatment of infections caused by organisms resistant to other aminoglycosides because of their ability to degrade them. Peak concentrations on 15 mg/kg once daily administration should exceed 45 mg/L, and trough concentration of <5 mg/L should be maintained to achieve therapeutic effects.

Clinical Use

Amikacin, 1-N-amino-α-hydroxybutyrylkanamycin A(Amikin), is a semisynthetic aminoglycoside first preparedin Japan. The synthesis formally involves simple acylationof the 1-amino group of the deoxystreptamine ring ofkanamycin A with L-AHBA. This particular acyl derivativeretains about 50% of the original activity of kanamycin Aagainst sensitive strains of Gram-negative bacilli. The LAHBAderivative is much more active than the D-isomer.The remarkable feature of amikacin is that it resists attackby most bacteria-inactivating enzymes and, therefore, is effectiveagainst strains of bacteria that are resistant to otheraminoglycosides, including gentamicin and tobramycin.In fact, it is resistant to all known aminoglycoside-inactivatingenzymes, except the aminotransferase that acetylates the6 amino group and the 4'-nucleotidyl transferase thatadenylylates the 4'-hydroxyl group of aminoglycosides.
Preliminary studies indicate that amikacin may be lessototoxic than either kanamycin or gentamicin. Higherdosages of amikacin are generally required, however, for the treatment of most Gram-negative bacillary infections. Forthis reason, and to discourage the proliferation of bacterialstrains resistant to it, amikacin currently is recommended forthe treatment of serious infections caused by bacterialstrains resistant to other aminoglycosides.

Side Effects

Distribution
The apparent volume of distribution indicates distribution throughout the extracellular water. Following an intravenous bolus of 0.5 g, peak concentrations in blister fluid were around 12 mg/L, with a mean elimination half-life of 2.3 h. In patients with impaired renal function, penetration and peak concentration increased linearly with decrease in creatinine clearance.
In patients with purulent sputum, a loading dose of 4 mg/kg intravenously plus 8 h infusions of 7–12 mg/kg produced sputum concentrations around 2 mg/L, with a mean sputum:serum ratio of 0.15. With brief infusions over 10 min for 7 days, sputum concentrations of around 9% of the simultaneous serum values have been found.
Concentrations in the CSF of adult volunteers receiving 7.5 mg/kg intramuscularly were less than 0.5 mg/L and virtually the same in patients with meningitis. Rather higher, but variable, concentrations up to 3.8 mg/L have been found in neonatal meningitis.
Amikacin crosses the placenta, and concentrations of 0.5–6 mg/L have been found in the cord blood of women receiving 7.5 mg/kg in labor. Concentrations of 8 mg/L and 16.8 mg/L were reached in the fetal lung and kidney, respectively, after a standard dose of 7.5 mg/kg given to healthy women before therapeutic abortion.
Excretion
Only 1–2% of the administered dose is excreted in the bile, with the remainder excreted in the urine, producing urinary concentrations of 150–3000 mg/L. Renal clearance is 70–84 mL/min, and this, with the ratio of amikacin to creatinine clearance (around 0.7), indicates that it is filtered and tubular reabsorption is insignificant. Accumulation occurs in proportion to reduction in renal function, although there may be some extrarenal elimination in anephric patients. The mean plasma half-life in patients on hemodialysis was around 4 h, while that on peritoneal dialysis was 28 h.
In patients receiving 500 mg/kg preoperatively, concentrations in gallbladder wall reached 34 mg/L and in bile 7.5 mg/L in some patients. In patients given 500 mg intravenously 12 h before surgery and 12 hourly for four doses thereafter, the mean bile:serum ratio 1 h after the dose was around 0.4.
Ototoxicity
Neurosensory hearing loss (mainly high-tone deafness) and labyrinthine injury have been detected, but have seldom been severe. High-frequency hearing loss and vestibular impairment have been described in about 5% of patients and conversational loss in about 0.5%; more in patients monitored audiometrically (29%) and by caloric testing (19%).
Patients with high-tone hearing loss have generally received more drug and for longer than patients without; in patients receiving long-term treatment for tuberculosis no other factors were associated with the development of ototoxicity. On multiple daily dosing, over half the patients with peak serum concentrations exceeding 30 mg/L or trough concentrations exceeding 10 mg/L developed cochlear damage; here, the main contributory factor was previous treatment with other aminoglycosides.
Nephrotoxicity
Impairment of renal function, usually mild or transient, has been observed in 3–13% of patients, notably in the elderly or those with pre-existing renal disorders or treated concurrently or previously with other potentially nephrotoxic agents.
Other reactions
Adverse effects common to aminoglycosides occur, including hypersensitivity, gastrointestinal disturbances, headache, drug fever, peripheral nervous manifestations, eosinophilia, mild hematological abnormalities and disturbed liver function tests without other evidence of hepatic derangement.

Safety Profile

Poison by intravenous,intraperitoneal, and intramuscular routes. Moderately toxicby intraperitoneal route. An experimental teratogen. Whenheated to decomposition it emits toxic fumes of NOx.

Synthesis

Amikacin, O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-[6-amino-6- deoxy-α-D-glucopyranosyl-(1→6)]-N3 -(4-amino-L-2-hydroxybutyryl)-2-deoxy-L-streptamine (3.4.10), is a semisynthetic antibiotic that is synthesized from kanamycin (3.4.6). The primary amino group in this molecule is previously protected by acylating it with N- (benzoyloxycarbonyloxy) succinimide in dimethylformamide, after which the resulting product (32.4.9) is treated with an ester synthesized from N-hydroxysuccinimide and benzyloxycarbonylamino-α-l-(?) hydroxybutyric acid, and as a result the 4-amino group of the streptamine region of the molecule is selectively acylated. Further removal of two benzyloxycarbonylamine protective groups in the traditional manner, via hydrogen reduction using a palladium on carbon catalyst, forms the desired amikacin (32.4.10).

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: increased risk of nephrotoxicity with colistimethate or polymyxins and possibly cephalosporins; increased risk of ototoxicity and nephrotoxicity with capreomycin or vancomycin.
Ciclosporin: increased risk of nephrotoxicity.
Cytotoxics: increased risk with platinum compounds of nephrotoxicity and possibly of ototoxicity
Diuretics: increased risk of ototoxicity with loop diuretics.
Muscle relaxants: enhanced effects of nondepolarising muscle relaxants and suxamethonium.
Parasympathomimetics: antagonism of effect of neostigmine and pyridostigmine.
Tacrolimus: increased risk of nephrotoxicity.

Metabolism

Amikacin's structure has been altered to reduce the possible route of enzymatic deactivation, thus reducing bacterial resistance. Many strains of Gram-negative organisms resistant to gentamicin and tobramycin have shown to be sensitive to amikacin in vitro.

Metabolism

Amikacin diffuses readily through extracellular fluids and has been found in cerebrospinal fluid, pleural fluid, amniotic fluid and in the peritoneal cavity following parenteral administration. It is excreted in the urine unchanged, primarily by glomerular filtration.