The pharmacokinetics of azithromycin in human serum and tissues

Abstract

The pharmacokinetics of azithromycin, a new azalide antibiotic, were examined in man. Approximately 37% of a single oral dose of 500 mg was bioavailable and produced a peak serum concentration of 0.4 mg/l. Multiple dose regimens (two doses of 500 mg separated by 12 h and followed by 500 mg qds for five days, or two doses of 250 mg separated by 12 h and followed by 250 mg qds for nine days) produced only slight increases in peak serum concentrations. The serum protein binding of azithromycin declined from about 50% at 0.02 mg/l to 12% at 0.5 mg/l. Tissue concentrations of azithromycin were much higher than serum concentrations. After two 250 mg doses 12 h apart, peak azithromycin concentrations exceeded 3 mg/kg in prostate, tonsil and many other tissues. Concentrations in tissues declined with apparent half-lives of 2.3 days in prostate and 3.2 days in tonsil. The high tissue concentrations suggest that proposed standard dosage regimens of 500 mg qds on day 1 followed by 250 mg qds for four days, or three daily dosages of 500 mg, will produce tissue concentrations above 3 mg/kg in a variety of tissues. Since these tissue concentrations exceed the MICs of relevant pathogens, these dosage regimens should be effective against respiratory tract and soft-tissue infections. A single 1 g dose may be effective in the treatment of many sexually transmitted diseases.

Use of antimicrobials and risk of type 1 diabetes in a population-based mother–child cohort

“…Unexpectedly, the maternal use of quinolones (ciprofloxacin, levofloxacin and norfloxacin), phenoxymethyl penicillins or macrolides (azithromycin, clarithromycin and roxithromycin) before pregnancy was related to the risk of type 1 diabetes in the child. The macrolides used in our birth cohort are lipophilic and become concentrated in body fats and tissues to levels that greatly exceed those in plasma [9]. Quinolones complex with calcium, accumulate in bone [10], and remobilise when calcium is mobilised, such as during pregnancy or lactation.…”

Amino Acid Substitution in the Major Multidrug Efflux Transporter Protein AcrB Contributes to Low Susceptibility to Azithromycin in Haemophilus influenzae

“…AZM shows relatively stronger antibacterial activity for H. influenzae, with a superior tissue distribution effect, compared to conventional macrolides (17)(18)(19)(20)(21). Furthermore, AZM was reported to be effective even when administered over a short period with a small dose, owing to its extended half-life (22,23).…”

Single-dose azithromycin for acute otitis media: a pharmacokinetic/pharmacodynamic rationale

“…13 The prolonged elimination half-life (Ͼ60 hours) allows for once-daily dosing. 3 In a study of children with AOM, azithromycin 10 mg/kg administered on day 1 followed by 5 mg/kg on day 2 achieved mean peak middle-ear fluid concentrations of 8.6 and 9.4 µg/mL at 24 and 48 hours after the initial dose, respectively. 14 In contrast, at 48 hours after treatment, azithromycin concentrations in plasma were ∼300 times lower than those in middle-ear fluid.…”

“…The incorporation of a second, ionizable amine group has resulted in key improvements over erythromycin: in particular, greater tissue penetration and an extended halflife of Ͼ60 hours. 3 The net charge of the azithromycin molecule varies depending on the pH of the environment. A weak base at physiologic pH, azithromycin is essentially nonpolar and lipophilic, and able to penetrate cell membranes.…”