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

• Published in: Annals of nuclear medicine 2010-02, Vol.24 (2), p.83-87
• Main Authors: Arakawa, Ryosuke, Ito, Hiroshi, Okumura, Masaki, Morimoto, Takuya, Seki, Chie, Takahashi, Hidehiko, Takano, Akihiro, Suhara, Tetsuya
• Format: Article
• Language: English
• Subjects: Adult; Anti-Bacterial Agents - pharmacology; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Biological Transport - drug effects; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Carbon Radioisotopes; Clarithromycin - pharmacology; Dose-Response Relationship, Drug; Humans; Imaging; Male; Medicine; Medicine & Public Health; Nuclear Medicine; Original Article; Positron-Emission Tomography; Radiology; Verapamil - metabolism; Young Adult
• ISSN: 0914-7187; 1864-6433
• DOI: 10.1007/s12149-009-0336-3

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 [ 11 C]verapamil. Methods Two PET scanning with [ 11 C]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 K 1 values of [ 11 C]verapamil before administration of clarithromycin were 0.042–0.070 mL/cm 3 /min (0.054 ± 0.012) and those after administration were 0.037–0.066 mL/cm 3 /min (0.055 ± 0.013). No significant change in K 1 values of [ 11 C]verapamil was observed between before and after administration of clarithromycin ( P  = 0.85). Conclusion K 1 values of [ 11 C]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.