The inhibitory effects of fluoroquinolones on L-carnitine transport in placental cell line BeWo.
L-Carnitine plays an important role in lipid metabolism by facilitating the transport of long-chain fatty acids across the mitochondrial inner membrane followed by fatty acid beta-oxidation. It is known that members of the OCTN family play an important role in L-carnitine transport in the placenta. Investigation of drug-drug or drug-nutrient interaction in the placenta is important for establishment of safety drug medication during pregnancy. The aim of this study was to determine the effects of fluoroquinolones, inhibitors of OCTN2, on L-carnitine transport in the placenta which is known to have a high expression level of OCTN2. We investigated the inhibitory effect of five fluoroquinolones, ciprofloxacin (CPFX), gatifloxacin (GFLX), ofloxacin (OFLX), levofloxacin (LVFX) and grepafloxacin (GPFX), on L-carnitine transport mediated by OCTN2 in placental cell line BeWo cells. We found that all of the fluoroquinolones inhibited L-carnitine transport, GPFX being the strongest inhibitor. We also found that the inhibitory effects of LVFX and GPFX depended on their existence ratio of zwitterionic forms as, we reported previously. Furthermore, we elucidated the LVFX transport mechanism in BeWo cells. LVFX was transported actively by transporters. However, we found that LVFX transport was Na+-independent and l-carnitine had no inhibitory effect on LVFX transport, suggesting that LVFX acts as inhibitor of OCTN2, not as a substrate for OCTN2.
Hirano
Takeshi
T
Department of Clinical Pharmaceutics & Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
Yasuda
Satoru
S
Osaka
Yuki
Y
Asari
Masaru
M
Kobayashi
Masaki
M
Itagaki
Shirou
S
Iseki
Ken
K
D001692:Biological Transport; D002331:Carnitine / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002939:Ciprofloxacin / Q000494:pharmacology; D004347:Drug Interactions; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D006801:Humans; D064704:Levofloxacin; D015242:Ofloxacin / Q000494:pharmacology; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000074058:Solute Carrier Family 22 Member 5
D024841:Fluoroquinolones; D027701:Organic Cation Transport Proteins; D010879:Piperazines; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002939:Ciprofloxacin; D064704:Levofloxacin; D012964:Sodium; D015242:Ofloxacin; C075375:grepafloxacin; D000077734:Gatifloxacin; D002331:Carnitine