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. 2010 Feb;24(2):83-7. doi: 10.1007/s12149-009-0336-3.

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 (K1) 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adult
  • Anti-Bacterial Agents / pharmacology*
  • Biological Transport / drug effects
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism*
  • Carbon Radioisotopes
  • Clarithromycin / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Positron-Emission Tomography*
  • Verapamil* / metabolism
  • Young Adult

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-Bacterial Agents
  • Carbon Radioisotopes
  • Verapamil
  • Clarithromycin