Page 846 - Basic _ Clinical Pharmacology ( PDFDrive )

832 SECTION VIII Chemotherapeutic Drugs

Pharmacokinetics vestibular function. Deafness may occur, especially in adults with
impaired renal function and prolonged elevation of drug levels.
Like all aminoglycosides, drugs of the neomycin group are poorly The sudden absorption of postoperatively instilled kanamycin
absorbed from the gastrointestinal tract. After oral administra- from the peritoneal cavity (3–5 g) has resulted in curare-like neu-
tion, the intestinal flora is suppressed or modified, and the drug romuscular blockade and respiratory arrest. Calcium gluconate
is excreted in the feces. Excretion of any absorbed drug is mainly and neostigmine can act as antidotes.
through glomerular filtration into the urine.
Although hypersensitivity is not common, prolonged appli-
cation of neomycin-containing ointments to skin and eyes has
Clinical Uses resulted in severe allergic reactions.

Neomycin is generally limited to topical and oral use due to toxicity
associated with parenteral use and higher resistance rates compared PLAZOMICIN
to other aminoglycosides. Kanamycin use is limited to treatment of
multi-drug-resistant tuberculosis, although alternate agents, such as Plazomicin is a new aminoglycoside under development and is
amikacin, may be preferred. It is no longer available in the USA. expected to undergo review by the U.S. Food and Drug Admin-
Paromomycin has been shown to be effective against visceral leish- istration in 2017. It has been studied in phase II clinical trials for
maniasis when given parenterally (see Chapter 52), and this serious treatment of urinary tract infections; phase III clinical trials are
infection may represent an important use for this drug. Paromomy- underway for treatment of carbapenem-resistant Enterobacteria-
cin can be used for intestinal Entamoeba histolytica infection and is ceae. It is a synthetic molecule derived from sisomicin, an ami-
sometimes used for intestinal infections with other parasites.
noglycoside no longer available,. Various structural modifications
have yielded a compound less susceptible to most aminoglycoside
A. Topical Administration modifying enzymes, thus retaining activity against aminogly-
Solutions containing 1–5 mg/mL neomycin have been used on coside-resistant pathogens. It appears to have similarly potent
infected surfaces or injected into joints, the pleural cavity, tissue in vitro activity against Enterobacteriaceae and displays two- to
spaces, or abscess cavities where infection is present. The total four-fold lower MICs against nonfermenting Gram-negative
amount of drug given in this fashion must be limited to 15 mg/kg/d bacilli (eg, P aeruginosa) when compared with gentamicin, tobra-
because at higher doses enough drug may be absorbed to produce mycin, and amikacin. It has activity similar to gentamicin against
systemic toxicity. Whether topical application for active infection staphylococci. A 15-mg/kg dose yields mean peak and trough con-
adds anything to appropriate systemic therapy is questionable. centrations of 113 mcg/mL and 0.43 mcg/mL, respectively. The
Ointments, often formulated as a neomycin-polymyxin-bacitracin half-life is about 4 hours, and it is being studied as a single daily
combination, can be applied to infected skin lesions or in the nares dose. Due to limited clinical experience, it is unclear whether the
for suppression of staphylococci but they are largely ineffective. toxicity profile will be similar to other aminoglycosides; however,
no ototoxicity or nephrotoxicity has been observed in early trials.
B. Oral Administration
In preparation for elective bowel surgery, 1 g of neomycin may
be given orally every 6–8 hours for 1–2 days, often combined ■ SPECTINOMYCIN
with 1 g of erythromycin base. This reduces the aerobic bowel
flora with little effect on anaerobes. In hepatic encephalopathy, Spectinomycin is an aminocyclitol antibiotic that is structurally
coliform flora can be suppressed by giving 1 g every 6–8 hours related to aminoglycosides. It lacks amino sugars and glycosidic
together with reduced protein intake, thus reducing ammonia bonds.
production. Use of neomycin for hepatic encephalopathy has been
CH 3 OH
largely supplanted by lactulose and other medications that are less O O
toxic. Use of paromomycin in the treatment of protozoal infec- HN CH 3
tions is discussed in Chapter 52.
HO O
C. Intravenous and Intramuscular Administration OH
NH O
When used intravenously, the standard dose for kanamycin is
15 mg/kg/day in two to three divided doses, whereas for treatment CH 3
of tuberculosis, 15 mg/kg is usually given intramuscularly as a sin- Spectinomycin
gle daily dose. In the case of once daily administration, kanamycin
peak concentrations are typically between 35 and 45 mcg/mL, Spectinomycin is active in vitro against many Gram-positive
while trough concentrations should be undetectable. and Gram-negative organisms, but it is used almost solely as
an alternative treatment for drug-resistant gonorrhea or gonor-
Adverse Reactions rhea in penicillin-allergic patients. The majority of gonococcal
isolates are inhibited by 6 mcg/mL of spectinomycin. Strains of
All members of the neomycin group have significant nephro- gonococci may be resistant to spectinomycin, but there is no
toxicity and ototoxicity. Auditory function is affected more than cross-resistance with other drugs used in gonorrhea. Notably, it is