Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
Laryngoscope. 2013 Dec;123(12):3172-7. doi: 10.1002/lary.24235. Epub 2013 Jul 29.
OBJECTIVES/HYPOTHESIS: Cisplatin produces toxic lesions to outer hair cells (OHCs) in the cochlear base but not in the apex. The objective of this study was to compare the pharmacokinetic profile of cisplatin in scala tympani (ST) perilymph in the cochlear base and apex, respectively.
In vivo animal study.
Forty-seven guinea pigs were given an intravenous bolus injection of an ototoxic dose of cisplatin. Ten to 240 minutes after cisplatin was given, blood, cerebrospinal fluid (CSF), and ST perilymph were aspirated within the same target time. ST perilymph was aspirated from the basal turn and from the apex of the cochlea by two different sampling techniques. Liquid chromatography with postcolumn derivatization was used for quantitative determination of the parent drug.
Ten minutes after administration, the concentration of cisplatin in ST perilymph was 4-fold higher in the basal turn of the cochlea than in the apex. At 30 minutes, the drug concentrations did not differ. At 60 minutes, the level of cisplatin in ST perilymph and blood UF was equivalent. The perilymph-blood ratio increased thereafter with time.
The pharmacokinetic findings of an early high concentration of cisplatin in the base of the cochlea and delayed elimination of cisplatin from ST perilymph compared to blood might correlate to the cisplatin-induced loss of OHCs in the base of the cochlea.
目的/假设：顺铂对耳蜗基底的外毛细胞（OHC）产生毒性损伤，但对耳蜗顶无损伤。本研究的目的是比较顺铂在耳蜗基底和顶部分别在鼓阶（ST）外淋巴液中的药代动力学特征。
体内动物研究。
47 只豚鼠静脉注射一剂耳毒性顺铂。在给予顺铂后 10 至 240 分钟，在相同的目标时间内从血液、脑脊液（CSF）和 ST 外淋巴液中抽取样本。通过两种不同的采样技术从耳蜗基底回和耳蜗顶部分别抽吸 ST 外淋巴液。采用柱后衍生化的液相色谱法对母体药物进行定量测定。
给药后 10 分钟，ST 外淋巴液中顺铂在耳蜗基底的浓度是耳蜗顶的 4 倍。30 分钟时，药物浓度没有差异。60 分钟时，ST 外淋巴液和血液 UF 中的顺铂水平相等。此后，随着时间的推移，顺铂的浓度比逐渐增加。
耳蜗基底顺铂早期浓度高和 ST 外淋巴液中顺铂延迟从血液中清除的药代动力学发现可能与顺铂诱导耳蜗基底 OHC 损失有关。
