Description

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).