The effect of sodium thiosulfate on ototoxicity and pharmacokinetics after cisplatin treatment in guinea pigs.
The effect of sodium thiosulfate (STS) on the pharmacokinetics and ototoxicity of cisplatin (CDDP) was investigated in guinea pigs. Animals received three intramuscular injections of 7.5 mg/kg CDDP separated by intervals of 5 days with or without STS (1,000 mg/kg) administered intraperitoneally immediately and 1 h after each injection of CDDP or 3 and 6 h later. When administered alone, CDDP caused total outer hair cell (OHC) loss in the basal and second turns of the cochlea. In the group administered CDDP and STS, damage to the OHCs was mild when STS was given concurrently, but was severe when STS was given 3 and 6 h later. Pharmacokinetics measured as free and total platinum (Pt) concentrations in plasma and total Pt concentration in perilymph was not affected after administration of STS with CDDP. These results suggest that an inactive Pt-thiosulfate complex is formed in plasma and is measured as a free Pt component which enters the perilymph via the blood-cochlear barrier. Two possible mechanisms are proposed by which STS reduces ototoxicity: entry of CDDP into target cells such as OHCs and strial marginal cells or binding to intracellular macromolecules of these cells is prevented.
Saito
T
T
Department of Otolaryngology, Fukui Medical School, Japan.
Zhang
Z J
ZJ
Manabe
Y
Y
Ohtsubo
T
T
Saito
H
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism; D013058:Mass Spectrometry; D013885:Thiosulfates / Q000494:pharmacology*
D000975:Antioxidants; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin