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


CONCLUSIONS
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.
Arakawa
Ryosuke
R
Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
Ito
Hiroshi
H
Okumura
Masaki
M
Morimoto
Takuya
T
Seki
Chie
C
Takahashi
Hidehiko
H
Takano
Akihiro
A
Suhara
Tetsuya
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D017291:Clarithromycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D014700:Verapamil / Q000378:metabolism; D055815:Young Adult
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D014700:Verapamil; D017291:Clarithromycin