Clarithromycin distribution

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. 

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. 

In an open, randomized, crossover study of the effects of oral omeprazole 20 mg/day for 7 days on the distribution of co-administered clarithromycin in the gastric juice in 18 male volunteers with H. pylori, short-term omeprazole increased the amount of clarithromycin transferred to the gastric juice, confirming synergy between these two drugs (34). 

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. 

Clarithromycin and its active metabolite, 14-hydroxycla-rithromycin, distribute widely and achieve high intracellular concentrations throughout the body. Tissue concentrations generally exceed serum concentrations. Concentrations in middle-ear fluid are 50% higher than simultaneous serum concentrations for clarithromycin and the active metabolite. Protein binding of clarithromycin ranges from 40 to 70% and is concentration dependent. 

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.)...

Despite some of the pharmacokinetic differences noted among these agents, they all exhibit wide distribution throughout the body. Of particular interest is the ability of these agents, especially azithromycin and clarithromycin, to accumulate within white blood cells. 

What is known suggests that clarithromycin, erythromycin and troleandomycin can inhibit the metabolism of methylprednisolone. The volume of distribution is also decreased. Clarithromycin may inhibit the metabolism of budesonide. ... 

Goddard AF, Jessa MJ, Barrett DA, Shaw PN, Idstrom JP, Cederberg C, Spiller RC (1996). Effect of omeprazole on the distribution of metronidazole, amoxicillin and clarithromycin in human gastric juice. Gastroenterology 111 358-367... 

---