[The clinical and pharmacokinetic evaluation of two-route chemotherapy with cisplatin and sodium thiosulfate in combination with angiotensin II].
Thirty-six courses of chemotherapy with cisplatin (CDDP) and sodium thiosulfate (STS) were performed in 31 patients with gynecologic cancer 2 weeks after operation under the hypertensive condition induced by angiotensin II (AT-II). One hundred-fifty mg of CDDP/body was intraperitoneally administered while the usual systolic blood pressure was increased to 130-140% by AT-II. The hypertension was maintained for 15 minutes after finishing CDDP infusion, then 8g of STS was intravenously infused immediately after the cessation of AT-II. The urinary Pt level measured 15 minutes after finishing CDDP infusion was extremely low at 1.37 +/- 0.47 micrograms/ml, in spite of the significantly high levels of plasma total Pt (7.83 +/- 0.85 micrograms/ml) and filtrable Pt (4.02 +/- 0.55 micrograms/ml). This suggests that, during renal vasoconstriction induced by AT-II, the renal blood flow as well as renal uptake of CDDP was decreased. Plasma filtrable Pt levels were measured at 15, 30, 60 and 120 minutes after intraperitoneal administration of CDDP. At 15 and 30 minutes a significantly higher blood concentration was found than in the control group (p less than 0.05). However, CDDP-induced toxicities of the bone marrow, liver, kidney and alimentary tract were not increased. The extreme vasoconstriction in the kidneys and other organs induced by AT-II might have protected these organs from the toxicities of CDDP despite the fact that STS infusion was delayed by 15 minutes after CDDP infusion. STS infused immediately after the cessation of AT-II could neutralize the CDDP preventing the occurrence of toxicities.(ABSTRACT TRUNCATED AT 250 WORDS)
Takizawa
K
K
Department of Obstetrics and Gynecology, Tokyo Women's Medical College.
Harada
M
M
Fujimaru
J
J
Matsushiro
N
N
Shima
Y
Y
Andoh
I
I
Satoh
M
M
Yokoo
I
I
Iguchi
T
T
Hirabayashi
K
K
D000804:Angiotensin II / Q000008:administration & dosage* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013885:Thiosulfates / Q000008:administration & dosage*; D014661:Vasoconstriction / Q000187:drug effects
D013885:Thiosulfates; D000804:Angiotensin II; C017717:sodium thiosulfate; D002945:Cisplatin