1. Introduction
Moxifloxacin,
sold under the brand name Avalos among others, is
an antibiotic used to treat a number of bacterial infections.( The American Society of Health-System
Pharmacists. 2017)
This includes pneumonia, conjunctivitis, endocarditis, tuberculosis,
and sinusitis. It is used as orally , parentally ,and as an eye drop.(
British Medical Association. 2015)
Common side effects of this drug include diarrhea, dizziness, and
headache. Severe side effects may include spontaneous tendon
ruptures, nerve damage, and worsening of myasthenia
gravis. Safety of use in pregnancy or breastfeeding
of this drug is unclear. Moxifloxacin belongs to
the fluoroquinolone family of medications. It kills the bacteria
through blocking their ability to duplicate DNA. (World Health Organization model list of essential
medicines, 2019)
1.1
History of Moxifloxacin
Moxifloxacin was first invented (United States patent) in 1991 by Bayer
A.G., and again in 1997 ( patentlens.net. 3
October 2006. ). Avalos was subsequently approved by the U.S.
Food and Drug Administration (FDA) for use in the United States in 1999 to
treat specific bacterial infections. It was ranked 140th within the top
200 prescribed drugs in the United States for 2007 (Pharmacy Times.,2009), Avalos generated sales of $697.3
million worldwide. Moxifloxacin is also manufactured by Alcon as Vitamix.
(Infection Control Today. 2003)
1.2 Pharmacology of drug
1.2
.1 Chemistry of Moxifloxacin
Moxifloxacin monohydrochloride is a slightly yellow to yellow
crystalline substance . It is synthesized in several steps, the first
involving the preparation of racemic 2,8-diazabicyclo[4.3.0]nonane
which is then resolved using tartaric acid. A suitably derivatized
quinoline carboxylic acid is then introduced, in the presence of DABCO,
followed by acidification to form moxifloxacin hydrochloride.( Peterson,
U. 2006 )
1.2.2 Mechanism of Action of Moxifloxacin
Moxifloxacin is a broad-spectrum antibiotic that is active
against both Gram-positive and Gram-negative bacteria. It
functions by inhibiting DNA gyrase, a type II topoisomerase, and
topoisomerase IV (Drlica K, Zhao, 1997), enzymes
necessary to separate bacterial DNA, thereby inhibiting cell replication .
1.2.3
Pharmacokinetic of the Drug
About 52% of an oral or intravenous dose of moxifloxacin is metabolized
via glucuronide and sulfate conjugation. The cytochrome P450 system is not
involved in moxifloxacin metabolism, and is not affected by moxifloxacin(World Health Organization ,2008). The sulfate
conjugate (M1) accounts for around 38% of the dose, and is eliminated primarily
in the feces. Approximately 14% of an oral or intravenous dose is converted to
a glucuronide conjugate (M2), which is excreted exclusively in the urine. Peak
plasma concentrations of M2 are about 40% those of the parent drug, while
plasma concentrations of M1 are, in general, less than 10% those of
moxifloxacin (Bayer, 2008).
In vitro studies
with cytochrome (CYP) P450 enzymes indicate that moxifloxacin does not inhibit
80 CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2, suggesting that moxifloxacin is
unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes.
The pharmacokinetics of moxifloxacin in pediatric subjects have not been
studied.
The elimination half-life of moxifloxacin is 11.5 to 15.6
hours (single-dose, oral). About 45% of an oral or intravenous dose of
moxifloxacin is excreted as unchanged drug (about 20% in urine and 25% in
feces). A total of 96 ± 4% of an oral dose is excreted as either unchanged drug
or known metabolites. The mean (± SD) apparent total body clearance and renal
clearance are 12 ± 2 L/h and 2.6 ± 0.5 L/h, respectively. The
CSF penetration of moxifloxacin is 70% to 80% in patients with meningitis
( Alffenaar J. W. C.; van Altena R.;
Bökkerink H. J (2009).
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