What is the bioavailability of azithromycin (Zithromax)?

From the Guidelines

Azithromycin has a bioavailability of approximately 37% when taken orally. This relatively low bioavailability is primarily due to incomplete absorption from the gastrointestinal tract and first-pass metabolism in the liver. The study 1 provides information on the dosage and administration of azithromycin, but does not directly address its bioavailability. However, it does mention that patients should be cautioned not to take azithromycin and aluminum- or magnesium-containing antacids simultaneously because the latter reduces the rate of absorption of azithromycin.

Key Points to Consider

• Food consumption can significantly affect azithromycin's bioavailability, with high-fat meals potentially reducing absorption by up to 50%
• Immediate-release formulations should be taken on an empty stomach, at least 1 hour before or 2 hours after meals
• Extended-release formulations (like Zmax) should be taken on an empty stomach at least 1 hour before or 2 hours after a meal, but can be taken with food if necessary to reduce gastrointestinal side effects
• Despite its relatively low bioavailability, azithromycin achieves high tissue concentrations due to its extensive distribution into tissues and cells, with concentrations in infected tissues often exceeding those in plasma by 10-100 times
• This property, combined with its long half-life, allows for once-daily dosing and short treatment courses for many infections.

Administration Considerations

• The dosage of azithromycin varies by age and weight, with infants aged <6 months requiring 10 mg/kg per day for 5 days, and adults requiring 500 mg on day 1, followed by 250 mg per day on days 2--5 1
• Patients with impaired hepatic function should be prescribed azithromycin with caution
• Monitoring of patients is advised when azithromycin is used concomitantly with agents metabolized by the cytochrome P450 enzyme system and with other drugs for which the pharmacokinetics change.

From the FDA Drug Label

The absolute bioavailability of azithromycin 250 mg capsules is 38%. The bioavailability of azithromycin is 38% for a 250 mg capsule dose 2.

From the Research

Bioavailability of Azithromycin

• The bioavailability of azithromycin is approximately 37% after a 500-mg oral dose 3, 4, 5.
• Concomitant administration of oral azithromycin with food significantly decreases drug bioavailability by 50% 5.
• The absolute bioavailability of azithromycin was found to be approximately one-half the value observed previously in healthy subjects, at 16.2% in a study involving subjects with ileostomies 6.

Factors Affecting Bioavailability

• Incomplete absorption is the primary cause of low oral bioavailability of azithromycin, rather than acid degradation or extensive first-pass metabolism 6.
• Acid degradation of azithromycin before absorption contributes to some loss in oral bioavailability 6.
• Ileal clearance (biliary plus intestinal excretion clearance) represents 21% of total clearance 6.

Pharmacokinetics

• Azithromycin has a large volume of distribution, with extensive and rapid distribution from serum into the intracellular compartments and tissues 3, 4, 5.
• Peak plasma concentrations of azithromycin are attained within approximately 2 hours after a single oral 500 mg dose 5.
• The mean terminal elimination half-life of azithromycin is 2 to 4 days 5, and up to 5 days 3.