Zithromax - Clinical Pharmacology

Azithromycin

• Zithromax - Drug Description
• Zithromax - Side Effects & Drug Interactions
• Zithromax - Warnings & Precautions
• Zithromax - Additional Info
• Zithromax - Overdosage & Contraindications
• Zithromax - Indications & Dosage
• Zithromax - Patient Info

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

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.

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%).