Effects of cisplatin on urinary thromboxane B2 excretion.
OBJECTIVE
Thromboxane A2 (TxA2) 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 TxA2 synthesis. To test this hypothesis, we measured urinary excretion of thromboxane B2 (TxB2), the stable inactive metabolite of TxA2, during and after cisplatin administration.


METHODS
The study included 16 patients with malignant disease who were scheduled to receive cisplatin (100 mg/m2) 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 TxB2 was measured.


RESULTS
There was a marked increase (4.5 +/- 1.6-fold; mean +/- SEM) in urinary TxB2 excretion in patients during and immediately after cisplatin infusion. This increase was significant compared with baseline and the control group.


CONCLUSIONS
High-dose cisplatin causes an acute increase in urinary excretion of TxB2. This likely represents enhanced intrarenal synthesis of TxA2, in response to an acute damaging effect of cisplatin on the kidneys. These findings warrant further studies to evaluate the renoprotective effect of anti-TxA2 intervention in patients receiving high-dose cisplatin.
Blöchl-Daum
B
B
Department of Clinical Pharmacology, Vienna University Hospital, Austria.
Pehamberger
H
H
Kurz
C
C
Kyrle
P A
PA
Wagner
O
O
Müller
M
M
Monitzer
B
B
Eichler
H G
HG
D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000652:urine; D013929:Thromboxane B2 / Q000652:urine*
D000970:Antineoplastic Agents; D013929:Thromboxane B2; D000118:Acetylglucosaminidase; D002945:Cisplatin