Clinical pharmacokinetics of oral azithromycin in epididymal tissue

Takuya Sadahira, Koichiro Wada, Kazuro Ikawa, Norifumi Morikawa, Masao Mitsui, Motoo Araki, Masachika Fujiyoshi, Ayano Ishii, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Research output: Contribution to journalArticle

Abstract

Objectives: Chlamydia trachomatis is one of the major pathogens causing acute epididymitis. Azithromycin (AZM) has a good efficacy against C. trachomatis; however, the ability of AZM to penetrate into human epididymal tissue has not yet been fully elucidated. Here, we examined the appropriate dosage of oral AZM for human epididymal tissue by site-specific pharmacokinetic/pharmacodynamic (PK/PD) analysis. Methods: Patients with prostate cancer who underwent orchiectomy were included in this study. All patients received a 1-g dose of AZM before orchiectomy. Both epididymal tissue and blood samples were collected during surgery, and the drug concentrations were measured by high-performance liquid chromatography. All concentration-time data were analyzed with a three-compartment model with first-order absorption and elimination processes to simulate AZM concentrations in serum and epididymal tissue. Results: A total of 10 patients were enrolled in the current study. For the observed values, the ratio of the epididymal concentration to the serum concentration was 5.13 ± 3.71 (mean ± standard deviation). For the simulated values, the maximum concentrations were 0.64 μg/mL at 2.42 h in serum and 1.96 μg/g at 4.10 h in epididymal tissue. The 24-h concentrations were 0.239 μg/mL in serum and 0.795 μg/g in epididymal tissue. Conclusions: The penetration of oral AZM into human epididymal tissue was examined to assess the potential application of AZM for the treatment of acute epididymitis. Based on the previous reports mentioning drug-susceptibility of C. trachomatis, multiple doses of oral AZM 1 g would be recommended for epididymitis based on the site-specific PK/PD.

Original languageEnglish
JournalJournal of Infection and Chemotherapy
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Azithromycin
Pharmacokinetics
Epididymitis
Chlamydia trachomatis
Orchiectomy
Serum
Pharmaceutical Preparations
Prostatic Neoplasms
High Pressure Liquid Chromatography

Keywords

  • Antimicrobial pharmacokinetics
  • Azithromycin
  • Epididymitis
  • Urogenital tract infection

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

@article{0e021fa92d144995b528fc75fa033b58,
title = "Clinical pharmacokinetics of oral azithromycin in epididymal tissue",
abstract = "Objectives: Chlamydia trachomatis is one of the major pathogens causing acute epididymitis. Azithromycin (AZM) has a good efficacy against C. trachomatis; however, the ability of AZM to penetrate into human epididymal tissue has not yet been fully elucidated. Here, we examined the appropriate dosage of oral AZM for human epididymal tissue by site-specific pharmacokinetic/pharmacodynamic (PK/PD) analysis. Methods: Patients with prostate cancer who underwent orchiectomy were included in this study. All patients received a 1-g dose of AZM before orchiectomy. Both epididymal tissue and blood samples were collected during surgery, and the drug concentrations were measured by high-performance liquid chromatography. All concentration-time data were analyzed with a three-compartment model with first-order absorption and elimination processes to simulate AZM concentrations in serum and epididymal tissue. Results: A total of 10 patients were enrolled in the current study. For the observed values, the ratio of the epididymal concentration to the serum concentration was 5.13 ± 3.71 (mean ± standard deviation). For the simulated values, the maximum concentrations were 0.64 μg/mL at 2.42 h in serum and 1.96 μg/g at 4.10 h in epididymal tissue. The 24-h concentrations were 0.239 μg/mL in serum and 0.795 μg/g in epididymal tissue. Conclusions: The penetration of oral AZM into human epididymal tissue was examined to assess the potential application of AZM for the treatment of acute epididymitis. Based on the previous reports mentioning drug-susceptibility of C. trachomatis, multiple doses of oral AZM 1 g would be recommended for epididymitis based on the site-specific PK/PD.",
keywords = "Antimicrobial pharmacokinetics, Azithromycin, Epididymitis, Urogenital tract infection",
author = "Takuya Sadahira and Koichiro Wada and Kazuro Ikawa and Norifumi Morikawa and Masao Mitsui and Motoo Araki and Masachika Fujiyoshi and Ayano Ishii and Masami Watanabe and Toyohiko Watanabe and Yasutomo Nasu",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jiac.2019.05.011",
language = "English",
journal = "Journal of Infection and Chemotherapy",
issn = "1341-321X",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Clinical pharmacokinetics of oral azithromycin in epididymal tissue

AU - Sadahira, Takuya

AU - Wada, Koichiro

AU - Ikawa, Kazuro

AU - Morikawa, Norifumi

AU - Mitsui, Masao

AU - Araki, Motoo

AU - Fujiyoshi, Masachika

AU - Ishii, Ayano

AU - Watanabe, Masami

AU - Watanabe, Toyohiko

AU - Nasu, Yasutomo

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objectives: Chlamydia trachomatis is one of the major pathogens causing acute epididymitis. Azithromycin (AZM) has a good efficacy against C. trachomatis; however, the ability of AZM to penetrate into human epididymal tissue has not yet been fully elucidated. Here, we examined the appropriate dosage of oral AZM for human epididymal tissue by site-specific pharmacokinetic/pharmacodynamic (PK/PD) analysis. Methods: Patients with prostate cancer who underwent orchiectomy were included in this study. All patients received a 1-g dose of AZM before orchiectomy. Both epididymal tissue and blood samples were collected during surgery, and the drug concentrations were measured by high-performance liquid chromatography. All concentration-time data were analyzed with a three-compartment model with first-order absorption and elimination processes to simulate AZM concentrations in serum and epididymal tissue. Results: A total of 10 patients were enrolled in the current study. For the observed values, the ratio of the epididymal concentration to the serum concentration was 5.13 ± 3.71 (mean ± standard deviation). For the simulated values, the maximum concentrations were 0.64 μg/mL at 2.42 h in serum and 1.96 μg/g at 4.10 h in epididymal tissue. The 24-h concentrations were 0.239 μg/mL in serum and 0.795 μg/g in epididymal tissue. Conclusions: The penetration of oral AZM into human epididymal tissue was examined to assess the potential application of AZM for the treatment of acute epididymitis. Based on the previous reports mentioning drug-susceptibility of C. trachomatis, multiple doses of oral AZM 1 g would be recommended for epididymitis based on the site-specific PK/PD.

AB - Objectives: Chlamydia trachomatis is one of the major pathogens causing acute epididymitis. Azithromycin (AZM) has a good efficacy against C. trachomatis; however, the ability of AZM to penetrate into human epididymal tissue has not yet been fully elucidated. Here, we examined the appropriate dosage of oral AZM for human epididymal tissue by site-specific pharmacokinetic/pharmacodynamic (PK/PD) analysis. Methods: Patients with prostate cancer who underwent orchiectomy were included in this study. All patients received a 1-g dose of AZM before orchiectomy. Both epididymal tissue and blood samples were collected during surgery, and the drug concentrations were measured by high-performance liquid chromatography. All concentration-time data were analyzed with a three-compartment model with first-order absorption and elimination processes to simulate AZM concentrations in serum and epididymal tissue. Results: A total of 10 patients were enrolled in the current study. For the observed values, the ratio of the epididymal concentration to the serum concentration was 5.13 ± 3.71 (mean ± standard deviation). For the simulated values, the maximum concentrations were 0.64 μg/mL at 2.42 h in serum and 1.96 μg/g at 4.10 h in epididymal tissue. The 24-h concentrations were 0.239 μg/mL in serum and 0.795 μg/g in epididymal tissue. Conclusions: The penetration of oral AZM into human epididymal tissue was examined to assess the potential application of AZM for the treatment of acute epididymitis. Based on the previous reports mentioning drug-susceptibility of C. trachomatis, multiple doses of oral AZM 1 g would be recommended for epididymitis based on the site-specific PK/PD.

KW - Antimicrobial pharmacokinetics

KW - Azithromycin

KW - Epididymitis

KW - Urogenital tract infection

UR - http://www.scopus.com/inward/record.url?scp=85067924286&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067924286&partnerID=8YFLogxK

U2 - 10.1016/j.jiac.2019.05.011

DO - 10.1016/j.jiac.2019.05.011

M3 - Article

C2 - 31255523

AN - SCOPUS:85067924286

JO - Journal of Infection and Chemotherapy

JF - Journal of Infection and Chemotherapy

SN - 1341-321X

ER -