Hypothesis： To determine the pharmacokinetics of sodium thiosulfate in the inner ear perilymph following middle ear application in Guinea pigs. Background： Cisplatin chemotherapy is often associated with a dose-depe...Hypothesis： To determine the pharmacokinetics of sodium thiosulfate in the inner ear perilymph following middle ear application in Guinea pigs. Background： Cisplatin chemotherapy is often associated with a dose-dependent high frequency senso- rineural hearing loss. Sodium thiosulfate has been shown to reduce cisplatin-induced ototoxicity when given intravenously, but this may limit the tumoricidal effects of the chemotherapy. Recent animal studies looking at middle ear application of sodium thiosulfate have shown prevention of outer hair cell and hearing loss, but the perilymph pharmacokinetics have not yet been established. Methods： Twenty Guinea pig ears were split into two groups and administered sodium thiosulfate to the middle ear at either a concentration of 250 mg/mL or 50 mg/mL for 30 min. Perilymph samples were then obtained serially through the round window over 6 h. Sodium thiosulfate concentrations were obtained using high-pressure liquid chromatography. Results： The 250 mg/mL group had a maximum perilymph concentration of 7.27 mg/mL （±0.83） that decreased to 0.94 mg/mL （±0.03） over 6 h. The 50 mg/mL group had an initial concentration of 1.63 mg/mL （±0.17） and was undetectable after 1 h. The half-life of sodium thiosulfate within perilymph was 0.74 h. Conclusions： and Relevance： The results of this study show that sodium thiosulfate is capable of diffusing through round window and into the inner ear perilymph. Peak levels decline over several hours after exposure. This has a potential application as a localized therapy in the prevention of cisplatin induced ototoxicity.展开更多
Fe and Zn levels in perilymph in guinea pigs injected with gentamicin(GM)were examined in this experlment,and those leves were compared with their correspondents in CSF,serum andhairs.Preventive and therapeutic action...Fe and Zn levels in perilymph in guinea pigs injected with gentamicin(GM)were examined in this experlment,and those leves were compared with their correspondents in CSF,serum andhairs.Preventive and therapeutic actions of seabuckthorn oil and injective gastrodini to hearing losswe observed.The results showed:①Fe content in perilymph and hair in GM ototxic guinea Pigswas increased,and was decreased after prevention and treating. There was no obvious change in CSFand serum.②Zn content in perilymph was increased in GM ototoxic guinea pigs,and was furtherincreased after prevention.Zn contents in serum and hairs were significantly decreased.The resultssuggest that GM ototoxic reaction is related to increasing Fe contents,and elevation ot Zn content isrelated to the compensative reaction of the body.The cjamges of chemical elements in perilymph aremore important than those in CSF,serum and hairs for pathologic changes in the cochlea,seabuckthorn oil can prevent GM ototoxic reaction.展开更多
文摘Hypothesis： To determine the pharmacokinetics of sodium thiosulfate in the inner ear perilymph following middle ear application in Guinea pigs. Background： Cisplatin chemotherapy is often associated with a dose-dependent high frequency senso- rineural hearing loss. Sodium thiosulfate has been shown to reduce cisplatin-induced ototoxicity when given intravenously, but this may limit the tumoricidal effects of the chemotherapy. Recent animal studies looking at middle ear application of sodium thiosulfate have shown prevention of outer hair cell and hearing loss, but the perilymph pharmacokinetics have not yet been established. Methods： Twenty Guinea pig ears were split into two groups and administered sodium thiosulfate to the middle ear at either a concentration of 250 mg/mL or 50 mg/mL for 30 min. Perilymph samples were then obtained serially through the round window over 6 h. Sodium thiosulfate concentrations were obtained using high-pressure liquid chromatography. Results： The 250 mg/mL group had a maximum perilymph concentration of 7.27 mg/mL （±0.83） that decreased to 0.94 mg/mL （±0.03） over 6 h. The 50 mg/mL group had an initial concentration of 1.63 mg/mL （±0.17） and was undetectable after 1 h. The half-life of sodium thiosulfate within perilymph was 0.74 h. Conclusions： and Relevance： The results of this study show that sodium thiosulfate is capable of diffusing through round window and into the inner ear perilymph. Peak levels decline over several hours after exposure. This has a potential application as a localized therapy in the prevention of cisplatin induced ototoxicity.
文摘Fe and Zn levels in perilymph in guinea pigs injected with gentamicin(GM)were examined in this experlment,and those leves were compared with their correspondents in CSF,serum andhairs.Preventive and therapeutic actions of seabuckthorn oil and injective gastrodini to hearing losswe observed.The results showed:①Fe content in perilymph and hair in GM ototxic guinea Pigswas increased,and was decreased after prevention and treating. There was no obvious change in CSFand serum.②Zn content in perilymph was increased in GM ototoxic guinea pigs,and was furtherincreased after prevention.Zn contents in serum and hairs were significantly decreased.The resultssuggest that GM ototoxic reaction is related to increasing Fe contents,and elevation ot Zn content isrelated to the compensative reaction of the body.The cjamges of chemical elements in perilymph aremore important than those in CSF,serum and hairs for pathologic changes in the cochlea,seabuckthorn oil can prevent GM ototoxic reaction.
