Macrolide antibiotics bioavailability

Erythromycins are macrolide antibiotics produced by bacterial fermentation. Fluoiination of erythromycin has been studied as a strategy to insure better stability in acidic medium and/or to achieve better bioavailability. An erythromycin, fluorinated at C-8, flurithromycin, was launched several years ago. Its preparation involves an electrophilic fluorination, with CF3OF [119] or with an N-F reagent A/-fluorobenzenesulfonimide (NFSI) [120], of the 8,9-anhydroerythromy-cin-6,9-hemiacetal or of the erythronolide A (Fig. 44). 

Erythromycins are macrolide antibiotics produced by bacterial fermentation. Fluori-nation of erythromycin has been studied to ensure abetter stability in acidic medium and/or a better bioavailability. 

Macrolide antibiotics are administered orally, but many of them exhibit low and/or variable degrees of oral absorption, low serum concentrations, and short half-lives. Consequently, selection of semi-synthetic derivatives for development has often been guided by greater oral bioavailability, longer half-life, and higher and more prolonged concentrations in serum and tissues. The clinical pharmacokinetic parameters of several 16-membered macrolides have recently been reviewed [58, 233, 234],... 

Nelfinavir mesylate is a peptidomimetic drug that is effective in HIV-1 and HIV-2 wild-type and ZDV-resistant strains, with median effective dose concentrations ranging from 9 to 60 nM (95% effective dose, 0.04 mg/mL) (98). After IV administration, the elimination half-life of nelfinavir was approximately 1 hour. In combination with D4T, nelfinavir reduced HIV viral load by approximately 98% after 4 weeks. It is well tolerated when used with azole antifungals (ketoconazole, fluconazole, or itraconazole) or macrolide antibiotics (erythromycin, clarithromycin, or azithromycin) however, it causes diarrhea and other side effects common to nonnucleoside drugs. Following oral administration, nelfinavir peak levels in plasma ranged from 0.34 mg/mL (10 mg/kg in the dog) to 1.7 mg/mL (50 mg/kg in the rat). In the dog, nelfinavir was slowly absorbed, and bioavailability was 47%. The drug appeared to be metabolized in the liver, and the major excretory route was in feces. 

CIMETIDINE MACROLIDES- ERYTHROMYCIN t efficacy and adverse effects of erythromycin, including hearing loss t bioavailability Consider an alternative antibiotic, e.g. clarithromycin. Deafness has been reversible with cessation of erythromycin... 

Macrolides with 14- and 16-membered rings have been productive sources of semisynthetic derivatives that have significantly extended the utility of the mac-rolide class as important antibiotics. New semisynthetic derivatives have exhibited a variety of improved features, such as an expanded antimicrobial spectrum, increased potency, greater efficacy, better oral bioavailability, extended chemical... 

The need for proper interpretation of the high tissue/serum ratios of macrolides and their clinical relevance have been recently reviewed [257-259]. Numerous studies have been published demonstrating intracellular uptake of macrolides. This phenomenon helps to explain their antimicrobial activity against many pathogens which reside in an intracellular environment, such as species of Legionella, Chlamydia, Salmonella, staphylococci, and mycobacteria. If the compound is bioavailable, high tissue concentrations of antibiotic would permit better eradication of infections localized within that tissue. 

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