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Effects of cisplatin on urinary thromboxane B 2 excretion
Author(s) -
BlöchlDaum Brigitte,
Pehamberger Hubert,
Kurz Christine,
Kyrle PaulAlexander,
Wagner Oswald,
Müller Markus,
Monitzer Brigitte,
Eichler HansGeorg
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90055-1
Subject(s) - cisplatin , thromboxane a2 , urinary system , medicine , thromboxane b2 , excretion , concomitant , urine , thromboxane , metabolite , pharmacology , pharmacokinetics , endocrinology , chemotherapy , platelet
Purpose Thromboxane A 2 (TxA 2 ) is implicated in the pathogenesis of various forms of drug‐induced renal damage. Based on previous functional studies, we postulated that cis ‐dichlorodiammineplatinum (cisplatin) induces intrarenal TxA 2 synthesis. To test this hypothesis, we measured urinary excretion of thromboxane B 2 (TxB 2 ), the stable inactive metabolite of TxA 2 , during and after cisplatin administration. Patients and methods The study included 16 patients with malignant disease who were scheduled to receive cisplatin (100 mg/m 2 ) and 11 healthy subjects who received the same amount of fluid loading and the same concomitant medication as the patients but no cisplatin. Total urine output was collected in seven intervals from 24 hours before until 72 hours after the start of prehydration. Urinary immunoreactive TxB 2 was measured. Results There was a marked increase (4.5 ± 1.6‐fold; mean ± SEM) in urinary TxB 2 excretion in patients during and immediately after cisplatin infusion. This increase was significant compared with baseline and the control group. Conclusion High‐dose cisplatin causes an acute increase in urinary excretion of TxB 2 . This likely represents enhanced intrarenal synthesis of TxA 2 , in response to an acute damaging effect of cisplatin on the kidneys. These findings warrant further studies to evaluate the renoprotective effect of anti‐TxA 2 intervention in patients receiving high‐dose cisplatin. Clinical Pharmacology & Therapeutics (1995) 58 , 418–424; doi: