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Pharmacokinetics of Oral Azithromycin in Serum, Urine, Polymorphonuclear Leucocytes and Inflammatory vs Non-Inflammatory Skin Blisters in Healthy Volunteers.
Clin Drug Investig. 1998; 15(2):159-67.CD

Abstract

Two open-label studies were conducted to assess the serum, urine, polymorphonuclear (PMN) and red blood cell (RBC) pharmacokinetics of a 5-day course (1500mg total) of oral azithromycin. Inflammatory and non-inflammatory blisters were also induced to study the propensity of azithromycin to preferentially concentrate at a model infection site. 14 subjects participated in the two studies and tolerated azithromycin and the study methods well. Comodelling of the serum and urine data demonstrated very extensive distribution into peripheral compartments, low renal clearance (7% of total oral clearance) and an extended terminal half-life (79 hours). PMN leucocyte concentrations peaked at 119 mg/L following the final dose and remained above 60 mg/L 7 days after the final dose. The ratio of blister to serum AUCs was significantly higher in inflammatory (2.2) vs non-inflammatory (1.2) blisters (p < 0.02). The extensive uptake of azithromycin into PMNs coupled with the accumulation of azithromycin into an inflammatory compartment (e.g. infection site) support the hypothesis that PMN leucocytes laden with azithromycin migrate to sites of inflammation, thereby enhancing local concentrations. These studies further demonstrate the unique pharmacokinetic properties of azithromycin and its preferential delivery by phagocytes to the site of infection.

Authors+Show Affiliations

The Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital and The State University of New York at Buffalo School of Pharmacy, Buffalo, New York, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18370479

Citation

Ballow, C H., et al. "Pharmacokinetics of Oral Azithromycin in Serum, Urine, Polymorphonuclear Leucocytes and Inflammatory Vs Non-Inflammatory Skin Blisters in Healthy Volunteers." Clinical Drug Investigation, vol. 15, no. 2, 1998, pp. 159-67.
Ballow CH, Amsden GW, Highet VS, et al. Pharmacokinetics of Oral Azithromycin in Serum, Urine, Polymorphonuclear Leucocytes and Inflammatory vs Non-Inflammatory Skin Blisters in Healthy Volunteers. Clin Drug Investig. 1998;15(2):159-67.
Ballow, C. H., Amsden, G. W., Highet, V. S., & Forrest, A. (1998). Pharmacokinetics of Oral Azithromycin in Serum, Urine, Polymorphonuclear Leucocytes and Inflammatory vs Non-Inflammatory Skin Blisters in Healthy Volunteers. Clinical Drug Investigation, 15(2), 159-67.
Ballow CH, et al. Pharmacokinetics of Oral Azithromycin in Serum, Urine, Polymorphonuclear Leucocytes and Inflammatory Vs Non-Inflammatory Skin Blisters in Healthy Volunteers. Clin Drug Investig. 1998;15(2):159-67. PubMed PMID: 18370479.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics of Oral Azithromycin in Serum, Urine, Polymorphonuclear Leucocytes and Inflammatory vs Non-Inflammatory Skin Blisters in Healthy Volunteers. AU - Ballow,C H, AU - Amsden,G W, AU - Highet,V S, AU - Forrest,A, PY - 2008/3/29/pubmed PY - 2008/3/29/medline PY - 2008/3/29/entrez SP - 159 EP - 67 JF - Clinical drug investigation JO - Clin Drug Investig VL - 15 IS - 2 N2 - Two open-label studies were conducted to assess the serum, urine, polymorphonuclear (PMN) and red blood cell (RBC) pharmacokinetics of a 5-day course (1500mg total) of oral azithromycin. Inflammatory and non-inflammatory blisters were also induced to study the propensity of azithromycin to preferentially concentrate at a model infection site. 14 subjects participated in the two studies and tolerated azithromycin and the study methods well. Comodelling of the serum and urine data demonstrated very extensive distribution into peripheral compartments, low renal clearance (7% of total oral clearance) and an extended terminal half-life (79 hours). PMN leucocyte concentrations peaked at 119 mg/L following the final dose and remained above 60 mg/L 7 days after the final dose. The ratio of blister to serum AUCs was significantly higher in inflammatory (2.2) vs non-inflammatory (1.2) blisters (p < 0.02). The extensive uptake of azithromycin into PMNs coupled with the accumulation of azithromycin into an inflammatory compartment (e.g. infection site) support the hypothesis that PMN leucocytes laden with azithromycin migrate to sites of inflammation, thereby enhancing local concentrations. These studies further demonstrate the unique pharmacokinetic properties of azithromycin and its preferential delivery by phagocytes to the site of infection. SN - 1173-2563 UR - https://www.unboundmedicine.com/medline/citation/18370479/full_citation L2 - https://dx.doi.org/10.2165/00044011-199815020-00009 DB - PRIME DP - Unbound Medicine ER -
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