Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses

Keith Melvin Olsen, Gerardo S. San Pedro, Larry P. Gann, Paul O. Gubbins, David M. Halinski, G. Douglas Campbell

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 124, 172, 244, 340, and 508 h after the first dose was administered. Azithromycin concentrations in epithelial lining fluid (ELF), alveolar macrophages, peripheral blood monocytes, and serum were measured by high- performance liquid chromatography. Azithromycin was extensively concentrated in cells and ELF. Drug concentrations in AMs (peak mean ± standard deviation, 464 ± 65 μg/ml) exceeded 80 μg/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (peak, 124 ± 28 μg/ml) exceeded 20 μg/ml up to 340 h (14 days). Azithromycin concentrations in ELF peaked at 124 h (3.12 ± 0.93 μg/ml) and were detectable up to 172 h (7 days), when they were 20 times the concurrent serum concentrations. Although the clinical significance of antibiotic concentrations in these compartments is unclear, the sustained lung tissue penetration and extensive phagocytic accumulation demonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellular or intracellular pulmonary infections.

Original languageEnglish (US)
Pages (from-to)2582-2585
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume40
Issue number11
StatePublished - Nov 1 1996

Fingerprint

Azithromycin
Healthy Volunteers
Pharmacokinetics
Lung
Phlebotomy
Alveolar Macrophages
Bronchoscopy
Bronchoalveolar Lavage
Serum
Monocytes
Appointments and Schedules
Epithelial Cells
High Pressure Liquid Chromatography
Anti-Bacterial Agents
Infection
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Olsen, K. M., San Pedro, G. S., Gann, L. P., Gubbins, P. O., Halinski, D. M., & Campbell, G. D. (1996). Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses. Antimicrobial Agents and Chemotherapy, 40(11), 2582-2585.

Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses. / Olsen, Keith Melvin; San Pedro, Gerardo S.; Gann, Larry P.; Gubbins, Paul O.; Halinski, David M.; Campbell, G. Douglas.

In: Antimicrobial Agents and Chemotherapy, Vol. 40, No. 11, 01.11.1996, p. 2582-2585.

Research output: Contribution to journalArticle

Olsen, KM, San Pedro, GS, Gann, LP, Gubbins, PO, Halinski, DM & Campbell, GD 1996, 'Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses', Antimicrobial Agents and Chemotherapy, vol. 40, no. 11, pp. 2582-2585.
Olsen KM, San Pedro GS, Gann LP, Gubbins PO, Halinski DM, Campbell GD. Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses. Antimicrobial Agents and Chemotherapy. 1996 Nov 1;40(11):2582-2585.
Olsen, Keith Melvin ; San Pedro, Gerardo S. ; Gann, Larry P. ; Gubbins, Paul O. ; Halinski, David M. ; Campbell, G. Douglas. / Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses. In: Antimicrobial Agents and Chemotherapy. 1996 ; Vol. 40, No. 11. pp. 2582-2585.
@article{0992424a650642b3aed9c8624e9d6a7a,
title = "Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses",
abstract = "The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 124, 172, 244, 340, and 508 h after the first dose was administered. Azithromycin concentrations in epithelial lining fluid (ELF), alveolar macrophages, peripheral blood monocytes, and serum were measured by high- performance liquid chromatography. Azithromycin was extensively concentrated in cells and ELF. Drug concentrations in AMs (peak mean ± standard deviation, 464 ± 65 μg/ml) exceeded 80 μg/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (peak, 124 ± 28 μg/ml) exceeded 20 μg/ml up to 340 h (14 days). Azithromycin concentrations in ELF peaked at 124 h (3.12 ± 0.93 μg/ml) and were detectable up to 172 h (7 days), when they were 20 times the concurrent serum concentrations. Although the clinical significance of antibiotic concentrations in these compartments is unclear, the sustained lung tissue penetration and extensive phagocytic accumulation demonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellular or intracellular pulmonary infections.",
author = "Olsen, {Keith Melvin} and {San Pedro}, {Gerardo S.} and Gann, {Larry P.} and Gubbins, {Paul O.} and Halinski, {David M.} and Campbell, {G. Douglas}",
year = "1996",
month = "11",
day = "1",
language = "English (US)",
volume = "40",
pages = "2582--2585",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses

AU - Olsen, Keith Melvin

AU - San Pedro, Gerardo S.

AU - Gann, Larry P.

AU - Gubbins, Paul O.

AU - Halinski, David M.

AU - Campbell, G. Douglas

PY - 1996/11/1

Y1 - 1996/11/1

N2 - The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 124, 172, 244, 340, and 508 h after the first dose was administered. Azithromycin concentrations in epithelial lining fluid (ELF), alveolar macrophages, peripheral blood monocytes, and serum were measured by high- performance liquid chromatography. Azithromycin was extensively concentrated in cells and ELF. Drug concentrations in AMs (peak mean ± standard deviation, 464 ± 65 μg/ml) exceeded 80 μg/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (peak, 124 ± 28 μg/ml) exceeded 20 μg/ml up to 340 h (14 days). Azithromycin concentrations in ELF peaked at 124 h (3.12 ± 0.93 μg/ml) and were detectable up to 172 h (7 days), when they were 20 times the concurrent serum concentrations. Although the clinical significance of antibiotic concentrations in these compartments is unclear, the sustained lung tissue penetration and extensive phagocytic accumulation demonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellular or intracellular pulmonary infections.

AB - The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 124, 172, 244, 340, and 508 h after the first dose was administered. Azithromycin concentrations in epithelial lining fluid (ELF), alveolar macrophages, peripheral blood monocytes, and serum were measured by high- performance liquid chromatography. Azithromycin was extensively concentrated in cells and ELF. Drug concentrations in AMs (peak mean ± standard deviation, 464 ± 65 μg/ml) exceeded 80 μg/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (peak, 124 ± 28 μg/ml) exceeded 20 μg/ml up to 340 h (14 days). Azithromycin concentrations in ELF peaked at 124 h (3.12 ± 0.93 μg/ml) and were detectable up to 172 h (7 days), when they were 20 times the concurrent serum concentrations. Although the clinical significance of antibiotic concentrations in these compartments is unclear, the sustained lung tissue penetration and extensive phagocytic accumulation demonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellular or intracellular pulmonary infections.

UR - http://www.scopus.com/inward/record.url?scp=0029958622&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029958622&partnerID=8YFLogxK

M3 - Article

VL - 40

SP - 2582

EP - 2585

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 11

ER -