1. Introduction
Erythromycin is one of the most common used macrolide antibiotics. Over the years after Abbott introduced Erythrocin® (erythromycin stearate) into the market, several generics and new brands have been introduced – generics in the form of different drug formulations and new brands in the form of different erythromycin salts.
All these derivatives have the same pharmacodynamics and mechanism of action, but differ tremendously in their pharmacokinetics.
This paper will give an introduction and a brief overview in the different stabilities and pharmacokinetics of the erythromycin salts and an introduction into new approaches in the field of macrolide antibiotics.
Table of Contents
1. Introduction 2
2. Erythromycin – a brief chemical description 4
2.1 Crystal structure and hygroscopicity 7
2.2 Mechanism of action 8
3. Derivatives of erythromycin base 9
3.1 Erythromycin stearate 10
3.2 Erythromycin ethyl succinate 10
3.3 Erythromycin estolate 11
3.4 Comparison between erythromycin base and estolate 13
4 Chemical derivatives of erythromycin 13
4.1 Roxithromycin 13
4.2 Clarithromycin 14
4.3 Azithromycin 14
4.4 Dirithromycin 15
4.5 Flurithromycin 16
4.6 Comparison of properties among the newer macrolides 17
5 Discussion and conclusions 19
References 21
2. Erythromycin – a brief chemical description
Figure 2.1 Advertisement for eryped® [3]
Erythromycin belongs to the chemical group of macrolide antibiotics (macros [greek] = great, -olid as the suffix for lactones). It's microbiological activity mainly covers bacterial infections of the respiratory tract and other infections with gram positive bacteria.
In the case of erythromycin base, the 14-linked lactone ring (Erythronolid) is conjugated with one basic amino sugar (Desopamine) and one neutral sugar (Cladinose).
Figure 2.2 Erythromycin base showing the aglycon (red), the basic amino sugar (green), and the neutral sugar (blue) [2]
Erythromycin was first discovered in 1952 in Streptomyces erythreus. The spectrum of activity is equal to penicillin. The antibiotic activity is linked to the presence of the desoxy sugars.
There are three known forms of erythromycin. The structure of erythromycin-A is the most common used in formulations and differs from erythromycin-B in the hydroxyl-group in position 13 of the lactone ring. Erythromycin-C is missing the methoxy-group in the cladinose sugar. [8]
Stability problems first were discovered when Erythrocin® was found to contain not the declared amount of erythromycin stearate.
The first stability problem with erythromycin is because of its deliquescence. This could be prevented if erythromycin is stored under accurate conditions.
Erythromycin has a poor water solubility and solutions decompose quicker if temperature is increased. Figure 2.1 shows the chemical degradation of erythromycin. The formation of the hemiketal is a dehydration and leads to the inactivation and loss of antibiotic activity. This step is highly pH sensitive.
Figure 2.3 Chemical degradation and inactivation of erythromycin [4]
Coumadin in pill form is taken orally. It needs to be stored at a controlled room temperature of 59 – 86 degrees and needs to be protecte...
...ucts are in the wrong conformation, the antibiotic will not work affectively in a patient’s system. This is especially useful when there are a set number of starting products, and one wishes to proceed down a chemical pathway in a certain number of steps. This reaction is also utilized as an “environmentally benign approach [to] solvation” (Morrison, et al., 2001) as well as in the production of “complex natural products” in chemical synthesis (Akiyama, et al., 2009). Robinson Annulation is a useful reaction, but not the simplest, so other types of enantioselective synthesis reactions have also been thought up, including “the Lewis acid catalyzed reaction of” regioselective compounds (Huffman, et al., 1985). Lastly, there is a Robinson Annulation Reaction involved in the synthesis of morphine, one of medicine’s basic “pain killer” medications (synarchive.com).
On the other hand, according to one study, the ability of macrolide antibiotics class to contraindicate with some of other drugs has been widely known. According to Westphal’s study in 2000: “Macrolides can induce their own hepatic biotransformation into nitrosoalkanes, which later form an inactive CYP3A4-iron-metabolite complexes to prevent the formation of the C...
Tobramycin is effective at reducing growth and reproduction of gram-negative bacteria. The bacteria P. aeruginosa, Klebsiella pneumoniae, Escherichia coli, Proteus, Serratia, Acinetobacter, Staphylococcus aureus are susceptible to Tobramycin. When treating enterococcal infections, which are part of the normal intestinal flora of humans, the addition of penicillin is needed. Tobramycin is used to treat external ocular infections, Urinary tract infection, Pseudomonas infection, Staphylococcus bacteria infection, and Respiratory Tract Infections. To reduce the creation of antibiotic-resistant bacteria, and to maintain the efficiency of Tobramycin, this ...
To help people with chronic anemia a synthetic version of Erythropoietin was produced called r-HuEPO, while provin...
The natural components of antibiotics have been used as local remedies long before humans understood the reasons why these sometimes-radical treatments worked. Penicillin became the first manufactured antibiotic after physician Alexander Fleming published articles regarding this bacteria-disabling mold in 1928. Come 1932, penicillin was commonly used to treat infected war injuries, saving the lives of unnumbered soldiers (Lewis). Since then, penicillin has b...
Antibiotics basically refer to chemical substances that can inhibit and destroy the growth of microorganisms (Gottileb,1976; Katz and Demain,1977). Antibiotic term was first used in 1942 by Selman Waksman to describe any substance produced by a microorganism which interfere with the growth of other microorganism (SA Waksman, 1947). Each antibiotic is produced by a relatively limited number of species and is inherited from specific set of genes. These are the products of secondary metabolism which can be produced commercially by microbial fermentation after active growth has declined. These compounds are generally synthesized in stationary phase especially idiophase (unbalanced growth phase) so these are sometimes called as idiolites(walker, 1974). Their formation is highly influenced not only by the growth conditions but also by the composition of the culture medium.
Throughout many generations the success of medicine has been dog-eared throughout history, from penicillin being created through colonized bacteria on an agar plate to chemotherapy being used to combat the ailments of cancer, we as a society rely a great deal on the effectiveness of medicine. Due to this realization one can agree that it is imperative that the medications that are being distributed and placed on the pharmaceutical market are tested and analyzed at all angles and perspectives to ensure they work effectively and successfully resulting in moderate to no side effects. The progressive industry of medicine has greatly increased since the early nineties thanks to the advancement in medical technology making
Compounding all of these solutions, the pharmaceutical industry needs to conduct extensive research on developing new antibiotics for various pathogenic bacteria by studying the bacterial structure. This will help scientists to formulate ways of counteracting the functions of the various constituents of bacteria.
The Merck Manuals. (2008). The Merck Manuals. Retrieved from The Merck Manuals Online Medical Library: http://www.merckmanuals.com/home/ag/sec07/ch107/ch107b.html
As we discussed above that pharmacokinetic and pharmacodynamics can be seen as two sides of the same coin in order to gain better understanding of their efficacy and safety profiles.” Generally it is possible to make fairly robust predictions of the pharmacokinetic profile in man using in vitro systems and preclinical pharmacokinetic studies. A previously published survey on the causes of failure in drug development indicated that inappropriate pharmacokinetics were a major cause such as; factors as low bioavailability due to high extraction or poor absorption characteristics, short elimination half-life leading to short duration of action and excessive variability due to genetic or environmental factors. This observation has led to an increased emphasis on pharmacokinetic input to the drug discovery process throughout the pharmaceutical industry. However, it is important to realise that this may only permit the rejection of compounds to b...
Penicillin, derived from the mold Penicillium, is the first antibiotic to successfully treat bacterial infections on humans. It was accidentally discovered by scientist, Alexander Fleming. While Fleming was growing Staphylococcus, a serious and often deadly infection, in a dish, he noticed the bacteria had stopped growing after a mold found its way
In the last decade, the number of prescriptions for antibiotics has increases. Even though, antibiotics are helpful, an excess amount of antibiotics can be dangerous. Quite often antibiotics are wrongly prescribed to cure viruses when they are meant to target bacteria. Antibiotics are a type of medicine that is prone to kill microorganisms, or bacteria. By examining the PBS documentary Hunting the Nightmare Bacteria and the article “U.S. government taps GlaxoSmithKline for New Antibiotics” by Ben Hirschler as well as a few other articles can help depict the problem that is of doctors prescribing antibiotics wrongly or excessively, which can led to becoming harmful to the body.
Discovery and Development of Penicillin. (2014, April 4). Retrieved from American Chemical Society International Historic Chemical Landmarks: https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html
The discovery of antibiotics is attributed to Alexander Fleming who discovered the first antibiotic to be commercially used (Penicillin) in approximately 1928. An antibiotic, also known as an antimicrobial, is a medication that is taken in order to either destroy or slow the growth rate of bacteria. Antibiotics are integral to the success of many medical practises, such as; surgical procedures, organ transplants, the treatment of cancer and the treatment of the critically ill. (Ramanan Laxminarayan, 2013)