Abstract
The concentrations of azithromycin in polymorphonuclear leukocytes (PMNLs), monocytes, erythrocytes, and plasma were measured in six healthy volunteers after the last treatment of a 3-day regimen of 500 mg once daily. Marked enrichment of azithromycin was found in PMNLs and monocytes. The drug concentrations after the last dose amounted to 114 +/- 43 (mean +/- standard deviation) mg/liter at 12 h in PMNLs and 34 +/- 17 mg/liter at 6 h in monocytes. Fourteen days thereafter, azithromycin was still detectable in the PMNLs at 53 +/- 34 mg/liter and in the monocytes at 1 +/- 2 mg/liter, although the drug was no longer detectable in plasma (< 0.02 mg/liter). Maximum drug concentrations for azithromycin in plasma (0.40 +/- 0.30 mg/liter) and erythrocytes (0.15 +/- 0.05 mg/liter) at 3 h after the last administration were much lower and occurred earlier than those observed in the phagocytic cells. The mean enrichment factors (cellular/extracellular ratios) of azithromycin in phagocytes relative to plasma came to 231 +/- 150 and 3,924 +/- 584 at 3 and 120 h, respectively, for PMNLs and 83 +/- 55 and 523 +/- 285 at 3 and 120 h for monocytes, respectively, after the last dose. The phagocytosis tests with PMNLs separated from the blood of volunteers at various times after the last treatment confirmed the enhanced intracellular activity of these cells against staphylococci.
Full Text
The Full Text of this article is available as a PDF (203.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bonnet M., Van der Auwera P. In vitro and in vivo intraleukocytic accumulation of azithromycin (CP-62, 993) and its influence on ex vivo leukocyte chemiluminescence. Antimicrob Agents Chemother. 1992 Jun;36(6):1302–1309. doi: 10.1128/aac.36.6.1302. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Deuticke B. Properties and structural basis of simple diffusion pathways in the erythrocyte membrane. Rev Physiol Biochem Pharmacol. 1977;78:1–97. doi: 10.1007/BFb0027721. [DOI] [PubMed] [Google Scholar]
- Gladue R. P., Bright G. M., Isaacson R. E., Newborg M. F. In vitro and in vivo uptake of azithromycin (CP-62,993) by phagocytic cells: possible mechanism of delivery and release at sites of infection. Antimicrob Agents Chemother. 1989 Mar;33(3):277–282. doi: 10.1128/aac.33.3.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hand W. L., King-Thompson N. L. Membrane transport of clindamycin in alveolar macrophages. Antimicrob Agents Chemother. 1982 Feb;21(2):241–247. doi: 10.1128/aac.21.2.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hand W. L., King-Thompson N. L. Uptake of antibiotics by human polymorphonuclear leukocyte cytoplasts. Antimicrob Agents Chemother. 1990 Jun;34(6):1189–1193. doi: 10.1128/aac.34.6.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kinasewitz G., Wood R. G. Azithromycin versus cefaclor in the treatment of acute bacterial pneumonia. Eur J Clin Microbiol Infect Dis. 1991 Oct;10(10):872–877. doi: 10.1007/BF01975846. [DOI] [PubMed] [Google Scholar]
- Laufen H., Wildfeuer A. Kinetics of the uptake of antimicrobial agents by human polymorphonuclear leucocytes. Arzneimittelforschung. 1989 Feb;39(2):233–235. [PubMed] [Google Scholar]
- Laufen H., Wildfeuer A., Lach P. Mechanism of azithromycin uptake in human polymorphonuclear leucocytes. Arzneimittelforschung. 1990 Jun;40(6):686–689. [PubMed] [Google Scholar]
- Laufen H., Wildfeuer A., Räder K. Uptake of antimicrobial agents by human polymorphonuclear leucocytes. Arzneimittelforschung. 1985;35(7):1097–1099. [PubMed] [Google Scholar]
- Riedel K. D., Wildfeuer A., Laufen H., Zimmermann T. Equivalence of a high-performance liquid chromatographic assay and a bioassay of azithromycin in human serum samples. J Chromatogr. 1992 May 8;576(2):358–362. doi: 10.1016/0378-4347(92)80212-9. [DOI] [PubMed] [Google Scholar]
- Wildfeuer A., Laufen H., Müller-Wening D., Haferkamp O. Interaction of azithromycin and human phagocytic cells. Uptake of the antibiotic and the effect on the survival of ingested bacteria in phagocytes. Arzneimittelforschung. 1989 Jul;39(7):755–758. [PubMed] [Google Scholar]
- Wildfeuer A., Laufen H., Zimmermann T. Distribution of orally administered azithromycin in various blood compartments. Int J Clin Pharmacol Ther. 1994 Jul;32(7):356–360. [PubMed] [Google Scholar]
- Zuckerman S. H., Douglas S. D. Dynamics of the macrophage plasma membrane. Annu Rev Microbiol. 1979;33:267–307. doi: 10.1146/annurev.mi.33.100179.001411. [DOI] [PubMed] [Google Scholar]