Erythromycin distribution

Erythromycin distributes widely in the body with residue levels in tissues generally exceeding those in serum. Both hepatic and renal routes of elimination of erythromycin are significant and it undergoes enterohepatic circulation. Elimination of erythromycin in relatively high levels in the feces may follow its oral administration. As with almost all macrolides, the principal metabolic pathway of erythromycin is by A-desmethylation of the desosamine sugar (107). 

Distribution Erythromycin distributes well to all body fluids except the cerebrospinal fluid (CSF). It is one of the few antibiotics that diffuses into prostatic fluid and has the unique characteristic of accumulating in macrophages. It concentrates in the liver. Inflammation allows for greater tissue penetration. Similarly, clarithromycin and azithromycin are widely distributed in tissues. Serum levels of azithromycin are low the drug is concentrated in neutrophils, macrophages, and fibroblasts. 

Triazolam is distributed quickly because of its high lipophilicity, and thus it has a short duration of effect. Erythromycin, nefazodone, fluvoxamine, and ketoconazole reduce the clearance of triazolam and increase plasma concentrations. 

Another basic drug where minor structural modification results in a dramatic increase in volume of distribution is the macrolide antibiotic, azithromycin. The traditional agent in this class is erythromycin, which contains one basic nitrogen, in the sugar side-chain. 

The macrolides are orally absorbed but they are acid-labile. They therefore need to be administered in acid-resistant capsules or as acid-resistant esters. The macrolides are widely distributed into all fluids except the CNS. Protein binding is about 90%. They are eliminated via biliary excretion with extensive enterohepatic circulation. Elimination half-lives vary from 1.4 h for erythromycin to 40-60 h for azithromycin. 

Drug A Amount Administered 420 mg Plasma Concentration 0.01 mg/mL Volume of Distribution 420 mg -+- 0.01 mg/mL = 42,000 mL = 42 L Indication Uniform distribution Examples Erythromycin lithium... 

Disease that is segmental or lobar in its distribution is usually caused by Streptococcus pneumoniae (pneumococcus). Haemophilus influenzae is a rare cause in this group, although it more often leads to exacerbations of chronic bronchitis and does cause pneumonia in patients infected with HIV. Benzyl-penicillin i.v. or amoxicillin p.o. are the treatments of choice if pneumococcal pneumonia is very likely alternatively, use erythromycin/clarithromycin in a penicillin-allergic patient. Seriously ill patients are best given benzylpenicillin (to cover the pneumococcus) plus ciprofloxacin (to cover Haemophilus and atypical pathogens). Where penicillin-resistant pneumococci are prevalent, i.v. cefotaxime is a reasonable best guess choice. 

The macrolides distribute well and tissue concentrations may be higher than serum concentrations. Erythromycin concentrates and is active in leukocytes because of its high lipid solubility and ion trapping. The of erythromycin is 3.7-7.21/kg in adult horses and foals. The protein binding is low. The hepatic clearance of the macrolides may be slower in animals of up to 1 month of age than in adult animals. 

Among the many antibiotics isolated from the actinomycetes isthe group of chemically related compounds called the mac-mlides. In I9S0, picromycin, the first of this group to be identified as a macrolide compound, was first reported. In 1952. erythromycin and carbomycin were reported us new antibiotics, and they were followed in subsequent years by other macrolides. Currently, more than 40 such compounds ate known, and new ones are likely to appear in the future. Of all of these, only two, erythromycin and oleandomycin, have been available consistently for medical use in the United States. In recent years, interest has shifted away from novel macrolides isolated from soil samples (e.g.,. spiramycin, josamycin, and rosamicin), all of which thus far have proved to be clinically inferior to erythromycin and semisynthetic derivatives of erythromycin (e.g., clarithromycin and azithromycin), which have superior pharmacokinetic properties due to their enhanced acid stability and improved distribution properties. 

IS% of the 14-hydroxy metabolite is excreted in the urine. Biliary excretion of clarithromycin is much lower than that of erythromycin. Clarithromycin is widely distributed into the tissues, which retain much higher concentrations than the plasma. Protein-binding fractions in the plasma range from 65 to 70%. The plasma half-life of clarithromycin is 4.3 hours. 

Schiigerl [105] reported several ELM-based apphcations for the extraction of alcohols, carboxylic acids, and antibiotics. Habaki et al. [106] studied the application of ELMs and SLMs in the extraction of erythromycin. The antibiotic molecules were able to cross the LMs without a carrier. Given their own data, as weh as the data of other authors, Habaki et al. concluded that the distribution coefficient of free erythromycin between the membrane phase and the feed solution for every LM studied was constant and independent on the H+ concentration in the feed solution. ELMs had lower extraction efficiencies for the erythromycin in comparison to SLMs [106]. 

The 1-decanol/water distribution coefEcient for the nonionized form of erythromycin A was equal to 122 and was shown to be independent of the pH of the feed and/or the stripping phase. The apparent 1-decanol/water distribution coefEcient, that is, the ratio of the total concentrations of erythromycin in the aqueous phase and 1-decanol, varied strongly with the pH of the aqueous phase and decreased from 122 at pH values above 10.0 to 10 at the pH value of 7.0. When feed phase and the stripping phase compartments are both stirred independently and the stirring rates range from 250 to 1500 rpm, 60-50% of the initial erythromycin amount was recovered in the stripping phase after 10 h [154]. The low fluxes, and thus long treatment periods, were attributed by the authors to low surface to volume ratio of the SLM system used, that is, limited interface area available for the erythromycin transport into the SLM. For practical application, the interfacial area of the SLM available for the transport seems to be one of the main factors to be optimized. 

Erythromycin (estolate is best absorbed oral form)—wide distribution into tissue and is eliminated mainly via biliary excretion. 

Lobster. Studies have been conducted to determine the pharmacokinetics of excretion, and the oral bioavailability of several drugs in adult lobsters of both sexes. Sulfadimethoxine and ormetoprim, which are used as a drug combination to treat various bacterial diseases, were studied separately and together. The usual dose ratio of the sulfadimethoxine ormetoprim combination is 42 4 mg/kg. Preliminary studies of the hemolymph concentration, and the tissue distribution at various times after intravascular and oral doses, were conducted with erythromycin, 50 mg/kg, in the free base form. Studies of the fate of phenol were conducted after intravascular administration of several doses. 

Figure 9a. Tissue distribution of " C-erythromycin as percent of dose after oral administration (5() mg/kg) to lobsters Homarus americanus). (n = 6).

Fig. 4. Whole-body autoradiograms showing the distribution of radioactivity 5 min after intravenous administration of C-clarithromycin (TE-031) and C-erythromycin (EM) (5 mg/kg) to rats. (From Kohno et al. [60], Fig, 2, p. 754.)...

For example, it is evident that antibiotic molecules are distributed randomly among ribosomes if the ribosomes are not clumped. Such an event would be expected to follow the Poisson distribution Pn (m) = m"e " /n, in which P is the probability that any antibiotic molecule ( ) at a binding site of the ribosome will be detected, and m is the mean number of drug molecules bound per ribosome. When the ratio of erythromycin molecules to ribosomal particles is one to one, it follows from the Poisson series that the proportion of ribosomes ... 

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