Paracellular transport properties of inner ear barriers do not account for cisplatin toxicity in the rat.
The interindividual variability for the ototoxic effect of the antineoplastic drug cisplatin has still to be explained. To examine if the variability can be related to differences in drug kinetics, the effect of cisplatin on the paracellular transport properties of the inner ear barriers was studied in vivo in cisplatin treated Long-Evans rats. The concentration of [3H]mannitol was followed in plasma, scala vestibuli perilymph, and endolymph after an intravenous infusion of the tracer. Cisplatin had no effect on paracellular transport of the inner ear barriers 3 days after administration of 8 mg/kg cisplatin. However, an interindividual variability for the transport of [3H]mannitol across the blood-perilymph barrier was evident, indicating a variability for the passive transport of solutes to the inner ear.
Laurell
G
G
Institut National de la Santé et de la Recherche Médicale U426, Dept.de Physiologie, Faculté Xavier Bichat, Université Paris 7, France.
Teixeira
M
M
Sterkers
O
O
Ferrary
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D001692:Biological Transport / Q000187:drug effects; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D004710:Endolymph / Q000378:metabolism; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008353:Mannitol / Q000008:administration & dosage / Q000378:metabolism; D010498:Perilymph / Q000378:metabolism; D051381:Rats; D012533:Scala Tympani / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium
D000970:Antineoplastic Agents; D014316:Tritium; D008353:Mannitol; D002945:Cisplatin