Zithromax - Clinical Pharmacology

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**** Sample was obtained 19 hours after a single 500 mg dose. The extensive tissue distribution was confirmed by examination of additional tissues and fluids (bone, ejaculum, prostate, ovary, uterus, salpinx, stomach, liver, and gallbladder). As there are no data from adequate and well-controlled studies of azithromycin treatment of infections in these additional body sites, the clinical significance of these tissue concentration data is unknown.

Following a regimen of 500 mg on the first day and 250 mg daily for 4 days, only very low concentrations were noted in cerebrospinal fluid (less than 0.01 µ g/ mL) in the presence of non-inflamed meninges. Following oral administration of a single 1200 mg dose (two 600 mg tablets), the mean maximum concentration in peripheral leukocytes was 140 µ g/ mL. Concentrations remained above 32 µ g/ mL for approximately 60 hr. The mean half-lives for 6 males and 6 females were 34 hr and 57 hr, respectively. Leukocyte to plasma Cmax ratios for males and females were 258 (± 77%) and 175 (± 60%), respectively, and the AUC ratios were 804 (± 31%) and 541 (± 28%), respectively. The clinical relevance of these findings is unknown.

Following oral administration of multiple daily doses of 600 mg (1 tablet/ day) to asymptomatic HIV-seropositive adults, mean maximum concentration in peripheral leukocytes was 252 µ g/ mL (± 49%). Trough concentrations in peripheral leukocytes at steady-state averaged 146 µ g/ mL (± 33%). The mean leukocyte to serum Cmax ratio was 456 (± 38%) and the mean leukocyte to serum AUC ratio was 816 (± 31%). The clinical relevance of these findings is unknown.

The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 µ g/ mL to 7% at 2 µ g/ mL. Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine.