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Clinical Pharmacology
CLINICAL PHARMACOLOGY
Pharmacokinetics Following oral administration, azithromycin is rapidly absorbed and widely distributed throughout the body. Rapid distribution of azithromycin into tissues and high concentration within cells result in significantly higher azithromycin concentrations in tissues than in plasma or serum. The 1 g single dose packet is bioequivalent to four 250 mg capsules. The pharmacokinetic parameters of azithromycin in plasma after dosing as per labeled recommendations in healthy young adults and asymptomatic HIV-seropositive adults (age 18-40 years old) are portrayed in the following chart:
MEAN (CV%) PK PARAMETER Text Continues Below
DOSE/ DOSAGE FORM (serum, except as indicated)
Subjects Day No. Cmax (µ g/ mL) Tmax (hr) C24 (g/ mL) AUC (ghr/ mL) T½ (hr)
Urinary Excretion
(% of dose) 500 mg/ 250 mg capsule 12 Day 1 0.41 2.5 0.05 2.6 a – 4.5
and 250 mg on Days 2-5 12 Day 5 0.24 3.2 0.05 2.1 a – 6.5
1200 mg/ 600 mg tablets 12 Day 1 0.66 2.5 0.074 6.8 b 40 –
%CV (62%) (79%) (49%) (64%) (33%)
600 mg tablet/ day 7 1 0.33 2.0 0.039 2.4 a
%CV 25% (50%) (36%) (19%)
7 22 0.55 2.1 0.14 5.8 a 84.5 -
%CV (18%) (52%) (26%) (25%) - 600 mg tablet/ day (leukocytes) 7 22 252 10.9 146 4763 a 82.8 -
%CV (49%) (28%) (33%) (42%) --a AUC0-24; b 0-last. In these studies (500 mg Day 1, 250 mg Days 2-5), there was no significant difference in the disposition of azithromycin between male and female subjects. Plasma concentrations of azithromycin following single 500 mg oral and i. v. doses declined in a polyphasic pattern resulting in an average terminal half-life of 68 hours. With a regimen of 500 mg on Day 1 and 250 mg/ day on Days 2-5, Cmin and Cmax remained essentially unchanged from Day 2 through Day 5 of therapy. However, without a loading dose, azithromycin Cmin levels required 5 to 7 days to reach steady-state. Page: 1 | 2 | 3 | 4 | 5 | Next >>
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