Distribution of platinum in blood and perilymph in relation to cisplatin induced ototoxicity in the guinea pig

Cisplatin, a platinum-based chemotherapeutic drug, has severe dose-limiting side effects which include ototoxicity. In this study, we investigate the ototoxic effects of cisplatin in relation to the concentration of platinum in whole blood, plasma and perilymph.Guinea pigs were equipped with a permanent round window electrode for electrocochleography and treated with cisplatin on a daily basis (1.5 mg/kg/day ip) until a 40 dB shift of the compound action potential (CAP) threshold (3 μV isoresponse criterion) at 8 kHz stimulation occurred. When this criterion was reached blood and perilymph was sampled and the total platinum concentration was measured.The number of days necessary to reach criterion threshold shift varied from 6 to 22. At this time, platinum concentration was found to be slightly more than 10 times higher in whole blood and plasma than in perilymph. While a significant correlation became apparent between threshold shift and total platinum concentration in whole blood and plasma, this was not the case for threshold shift and platinum concentration in perilymph.