Role of substance P in hypersensitivity reactions induced by paclitaxel, an anticancer agent.
The role of substance P in adverse pulmonary reactions induced by an anticancer agent paclitaxel was investigated in rats and humans who undertook post-operative chemotherapy for ovarian cancer. In rats, paclitaxel caused a marked plasma extravasation and edema in lungs with a concomitant decrease in arterial partial oxygen pressure, which were reversed by an NK1 antagonist LY303870. Substance P level in rat plasma and bronchoalveolar lavage fluid increased after paclitaxel injection. In 13 patients, plasma level of substance P but not histamine significantly (P < 0.05) increased during paclitaxel infusion. Therefore, substance P rather than histamine may be involved in paclitaxel hypersensitivity.
Sendo
Toshiaki
T
Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Itoh
Yoshinori
Y
Goromaru
Takeshi
T
Hirakawa
Toshio
T
Ishida
Mawako
M
Nakano
Hitoo
H
Oishi
Ryozo
R
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006632:Histamine / Q000097:blood; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010051:Ovarian Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000139:chemically induced; D012189:Retrospective Studies; D013373:Substance P / Q000032:analysis / Q000097:blood / Q000378:metabolism*
C096759:1-(N-(2-methoxybenzyl)acetylamino)-3-(1H-indol-3-yl)-2-(N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino)propane; D000970:Antineoplastic Agents; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D013373:Substance P; D006632:Histamine; D017239:Paclitaxel