Zithromax

[Azithromycin]

In asymptomatic HIV-seropositive adult subjects receiving 600-mg ZITHROMAX ® tablets once daily for 22 days, steady state azithromycin serum levels were achieved by Day 15 of dosing.

When azithromycin capsules were administered with food, the rate of absorption (Cmax) of azithromycin was reduced by 52% and the extent of absorption (AUC) by 43%. When the oral suspension of azithromycin was administered with food, the Cmax increased by 46% and the AUC by 14%. The absolute bioavailability of two 600 mg tablets was 34% (CV= 56%). Administration of two 600 mg tablets with food increased Cmax by 31% (CV= 43%) while the extent of absorption (AUC) was unchanged (mean ratio of AUCs= 1.00; CV= 55%).

The AUC of azithromycin in 250 mg capsules was unaffected by coadministration of an antacid containing aluminum and magnesium hydroxide with ZITHROMAX ® (azithromycin); however, the Cmax was reduced by 24%. Administration of cimetidine (800 mg) two hours prior to azithromycin had no effect on azithromycin absorption.

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When studied in healthy elderly subjects from age 65 to 85 years, the pharmacokinetic parameters of azithromycin (500 mg Day 1, 250 mg Days 2-5) in elderly men were similar to those in young adults; however, in elderly women, although higher peak concentrations (increased by 30 to 50%) were observed, no significant accumulation occurred.

The high values in adults for apparent steady-state volume of distribution (31.1 L/ kg) and plasma clearance (630 mL/ min) suggest that the prolonged half-life is due to extensive uptake and subsequent release of drug from tissues. Selected tissue (or fluid) concentration and tissue (or fluid) to plasma/ serum concentration ratios are shown in the following table:

AZITHROMYCIN CONCENTRATIONS FOLLOWING TWO 250 mg (500 mg) CAPSULES IN ADULTS TISSUE OR FLUID TIME AFTER DOSE (h) TISSUE OR FLUID CONCENTRATION (g/ g or µ g/ mL) 1 CORRESPONDING PLASMA OR SERUM LEVEL (g/ mL) TISSUE (FLUID) PLASMA (SERUM) RATIO 1
SKIN 72-96 0.4 0.012 35 LUNG 72-96 4.0 0.012 >100
SPUTUM* 2-4 1.0 0.64 2 SPUTUM** 10-12 2.9 0.1 30
TONSIL*** 9-18 4. 5 0. 03 >100 TONSIL*** 180 0.9 0.006 >100
CERVIX**** 19 2. 8 0. 04 70 1
High tissue concentrations should not be interpreted to be quantitatively related to clinical efficacy. The antimicrobial activity of azithromycin is pH related. Azithromycin is concentrated in cell lysosomes which have a low intraorganelle pH, at which the drug's activity is reduced. However, the extensive distribution of drug to tissues may be relevant to clinical activity. * Sample was obtained 2-4 hours after the first dose ** Sample was obtained 10-12 hours after the first dose. *** Dosing regimen of 2 doses of 250 mg each, separated by 12 hours.

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