Study on emetic response of CPT-11, a new anti-cancer drug, in dogs, ferrets and suncus.

Tukasuna, Kiyoshi; Yamashita, Noboru; Kasai, Yoshio; Kitano, Yutaka; Mor, Kazuhiko; Takahashi, Mariko; Usui, Chiharu; Hirohashi, Masaaki; Tamura, Kiyoshi

doi:10.1016/s0021-5198(19)38617-2

Cited by 2 publications

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“…In nonclinical studies, drug candidates sometimes induce histamine release in laboratory animals (Mori et al, 2000;Takasuna et al, 1992;Kojima et al, 1984). Because histamine release is potentially associated with serious adverse reactions such as anaphylaxis (Peavy and Metcalfe, 2008;White, 1990), careful evaluation is required.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, the dose levels that caused histamine release in dogs were 30 to 100 times lower than in rats (Mori et al, 2000). In addition, intravenous injections of fluoroquinolones, opioids, or neuromuscular blocking agents have been reported to cause severe hypotension in dogs with increasing blood histamine levels (Furuhata et al, 1998;Lee and Johnson, 1971;Robinson et al, 1988;Takasuna et al, 1992). Therefore, in vivo studies using dogs have been conducted generally to detect risks of drug-induced pseudo-allergic reactions.…”

Section: Introductionmentioning

confidence: 99%

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Effective <i>in vitro</i> evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells

Hamamura-Yasuno,

Kinoshita,

Goto

et al. 2024

J. Toxicol. Sci.

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Mas-related G-protein-coupled receptor X2 (MRGPRX2), expressed on mast cells, is associated with drug-induced pseudo-allergic reactions. Although it is well known that there are differences of sensitivity between species in the pseudo-allergic reactions, no platform for evaluating a human risk of the pseudo-allergic reactions observed in nonclinical studies has been established. Valemetostat tosylate, developed as an anti-cancer drug, induced histamine release in a nonclinical study with dogs. The purpose of the current study was to identify the mechanism and assess the human risk of valemetostat-tosylate-induced histamine release using dog and human MRGPRX2-expressing cells. In an experiment with human or dog MRGPRX2-expressing cells, valemetostat tosylate caused activation of human and dog MRGPRX2. Importantly, the EC 50 for dog MRGPRX2 was consistent with the C max value at which histamine release was observed in dogs. Furthermore, the EC 50 for human MRGPRX2 was ca. 27-fold higher than that for dog MRGPRX2, indicating a species difference in histamine-releasing activity. In a clinical trial, histamine release was not observed in patients receiving valemetostat tosylate. In conclusion, an in vitro assay using human and animal MRGPRX2-expressing cells would be an effective platform to investigate the mechanism and predict the human risk of histamine release observed in nonclinical studies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effective <i>in vitro</i> evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells

Hamamura-Yasuno,

Kinoshita,

Goto

et al. 2024

J. Toxicol. Sci.

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Protective Effects of Kampo Medicines and Baicalin against Intestinal Toxicity of a New Anticancer Camptothecin Derivative, Irinotecan Hydrochloride (CPT‐11), in Rats

Takasuna¹,

Kasai²,

Kitano³

et al. 1995

Japanese Journal of Cancer Research

106

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In clinical use, irinotecan hydrochloride (CPT‐11; 7‐ethyl‐10‐[4‐(piperidmo)‐l‐piperidino]carbonyl‐oxycamptothecin), a novel antitumor agent, causes a relatively high incidence of severe forms of diarrhea. We investigated whether baicalin, an inhibitor of β‐glucuronidase, which deconjugates the glucuronide of the active metabolite of CPT‐11, SN‐38 (7‐ethyl‐10‐hydorxycamptothecin), and Japanese herbal medicines (Kampo medicines) which contain baicalin can ameliorate CPT‐11‐induced intestinal toxicity in rats. CPT‐11 (60 mg/kg i.v. once daily for 4 consecutive days) induced intestinal toxicity characterized by diarrhea, loss of body weight, anorexia and disruption of intestinal epithelium. Treatment with baicalin (25 mg/kg p.o. twice daily) or Kampo medicines (TJ‐14 and TJ‐114; 1 g/kg p.o. twice daily) from the day before to 4 or 10 days after the start of CPT‐11 administration resulted in significantly decreased weight loss, improved anorexia and a delayed onset of diarrheal symptoms. Histological examination revealed that Kampo medicine‐treated animals had less damage to the intestinal epithelium and that damage was repaired more rapidly than in control rats. These results suggest that the prophylactic use of Kampo medicines (TJ‐14 and TJ‐114) may be of value against CPT‐11‐induced intestinal toxicity.

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Study on emetic response of CPT-11, a new anti-cancer drug, in dogs, ferrets and suncus.

Cited by 2 publications

References 0 publications

Effective <i>in vitro</i> evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells

Effective <i>in vitro</i> evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells

Protective Effects of Kampo Medicines and Baicalin against Intestinal Toxicity of a New Anticancer Camptothecin Derivative, Irinotecan Hydrochloride (CPT‐11), in Rats

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