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No inhibitory effect on P-glycoprotein function at blood–brain barrier by clinical dose of clarithromycin: a human PET study with [11C]verapamil

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Abstract

Objective

To investigate the effects of the clinical dose of clarithromycin, a substrate of P-glycoprotein (P-gp), on P-gp function using positron emission tomography (PET) with [11C]verapamil.

Methods

Two PET scanning with [11C]verapamil were performed before and after administration of 400 mg/day of clarithromycin on each of four healthy male subjects. The rate constant of transfer from plasma to brain (K 1) was estimated by integration plot method.

Results

K1 values of [11C]verapamil before administration of clarithromycin were 0.042–0.070 mL/cm3/min (0.054 ± 0.012) and those after administration were 0.037–0.066 mL/cm3/min (0.055 ± 0.013). No significant change in K1 values of [11C]verapamil was observed between before and after administration of clarithromycin (P = 0.85).

Conclusion

K1 values of [11C]verapamil were not changed by clinical dose administration of clarithromycin, suggesting that a clinical dose of clarithromycin does not affect P-gp function at the blood–brain barrier.

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Acknowledgments

We thank Mr. Katsuyuki Tanimoto, Mr. Takahiro Shiraishi and Mr. Toshio Miyamoto for their assistance in performing the PET experiments, and Ms. Yoshiko Fukushima for her help as clinical research coordinator at the National Institute of Radiological Sciences. We also thank Dr. Mizuno Kenji for the measurement of plasma concentration of clarithromycin at the Pharmacokinetics and Metabolism, Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co. Ltd.

Conflict of interest statement

This study was supported by a consignment expense for the Molecular Imaging Program on “Research Base for PET Diagnosis” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japanese Government. None of the authors has any conflicts of interest.

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Authors and Affiliations

  1. Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba, 263-8555, Japan

    Ryosuke Arakawa, Hiroshi Ito, Masaki Okumura, Takuya Morimoto, Chie Seki, Hidehiko Takahashi, Akihiro Takano & Tetsuya Suhara

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  1. Ryosuke Arakawa
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  2. Hiroshi Ito
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  3. Masaki Okumura
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  4. Takuya Morimoto
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  5. Chie Seki
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  6. Hidehiko Takahashi
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  7. Akihiro Takano
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  8. Tetsuya Suhara
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Corresponding author

Correspondence to Hiroshi Ito.

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Arakawa, R., Ito, H., Okumura, M. et al. No inhibitory effect on P-glycoprotein function at blood–brain barrier by clinical dose of clarithromycin: a human PET study with [11C]verapamil. Ann Nucl Med 24, 83–87 (2010). https://doi.org/10.1007/s12149-009-0336-3

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  • DOI: https://doi.org/10.1007/s12149-009-0336-3

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