Clinical Evaluation of Antiemetic Effects of 5-hydroxytryptamine Receptor type 3 (5HT&lt;sub&gt;3&lt;/sub&gt; Receptor) Antagonists Based on Changes in Eating Condition in Cancer Patients Receiving Chemotherapy

Okuyama, Kiyoshi; Yoshimoto, Koichi; Iwase, Osamu; Ozeki, Takeshi; Yamada, Yasuhiko

doi:10.1248/yakushi.128.649

Cited by 2 publications

(3 citation statements)

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“…Condition of Food Intake, and Occurrence of Nausea and Vomiting We evaluated food intake and occurrence of nausea and vomiting in the patients based on data recorded from beginning of administration of granisetron to the finish of urine collection. Our previously reported method was used to quantify the condition of food intake, 5) with some modifications. eating scores for consumption of all, half, 1/3, a little, and none were recorded as 5, 4, 3, 2, and 1, respectively, while nausea scores for none, a little, sometimes, continuing, and continuing serious were 5, 4, 3, 2, and 1, respectively.…”

Section: Calculation Of 5-ht 3 Receptor Occupancy Of Serotonin In Smamentioning

confidence: 99%

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Method for Individualized Evaluation of Antiemetic Effect Induced by 5-HT<sub>3</sub> Receptor Antagonist

Nakamura

Yokoyama

Yoshimoto

et al. 2013

Biological & Pharmaceutical Bulletin

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5-HT 3 receptor antagonists are widely used for prevention of chemotherapy-induced nausea and vomiting, though their antiemetic effects vary among patients. We investigated a method for evaluation of antiemetic effects in individual patients. We used the 5-HT 3 receptor occupancy of serotonin for our evaluation, which was estimated based on the plasma concentration of granisetron and concentration of serotonin near the 5-HT 3 receptor in the small intestine, obtained by measuring the urinary concentrations of granisetron and 5-hydroxyindoleacetic acid (5-HIAA)/creatinine (Cre). The mean cumulative percent for urinary excretion of granisetron at 24 h after administration and coefficient of variation were 16.19±6.30% and 38.91%, respectively. The time course of urinary concentration of 5-HIAA/Cre also varied among the patients. The value for 5-HT 3 receptor occupancy of serotonin without granisetron was higher than that prior to administration (blank), thus most treated patients had the possibility of induced emesis. In contrast, that with granisetron was lower than the blank value, indicating that those treated patients would not develop emesis. Furthermore, the estimated 5-HT 3 receptor occupancy of serotonin in the small intestine and actual individual patient condition corresponded well, showing the validity of our method. Our results suggest that it is possible to evaluate individual antiemetic effects by estimating the 5-HT 3 receptor occupancy of serotonin in the small intestine based on plasma concentrations of granisetron and serotonin near the 5-HT 3 receptor in the small intestine using noninvasive urine samples. This method of individual evaluation is considered to be useful and effective.Key words urinary 5-hydroxyindoleacetic acid; 5-HT 3 receptor occupancy; granisetron; 5-HT 3 receptor antagonist; antiemetic effect Chemotherapy-induced nausea and vomiting can lead to discontinuation of treatment and decrease the quality of life of affected patients. One of the main mechanisms of these adverse effects induced by antineoplastic agents is activation by serotonin of 5-HT 3 receptors, which exist on vagus nerve afferent fibers in the small intestine mucous membrane. With antineoplastic drug administration, serotonin is released from enterochromaffin cells, which synthesize and secrete this neurotransmitter, and stimulates 5-HT 3 receptors on adjacent vagal afferent nerves. Depolarization of the vagal afferent nerves stimulates the vomiting center in the brainstem and eventually induces a vomiting reflex.1) Therefore, the concentration of serotonin near 5-HT 3 receptors in the small intestine may be an indicator of the degree of emetic action. Serotonin is metabolized to 5-hydroxyindoleacetic acid (5-HIAA), which is subsequently excreted in urine. Moreover, a relationship between the frequency of vomiting and cumulative urinary excretion of 5-HIAA after administration of cisplatin (50 mg/m 2 ) has been reported.2) As a result, the urinary concentration of 5-HIAA may also be a helpful indicator of the degr...

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Section: Calculation Of 5-ht 3 Receptor Occupancy Of Serotonin In Smamentioning

confidence: 99%

“…4) Moreover, we previously reported that interindividual variations for eating scores were large in patients administered granisetron. 5) Thus, clinical difficulties may be encountered because of the wide interindividual variations in plasma concentrations and variable antiemetic effects of granisetron among patients.…”

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Method for Individualized Evaluation of Antiemetic Effect Induced by 5-HT<sub>3</sub> Receptor Antagonist

Nakamura

Yokoyama

Yoshimoto

et al. 2013

Biological & Pharmaceutical Bulletin

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“…The 5-hydroxytryptamine 3 (5-HT 3 ) receptors present in the gut are considered to be active sites for 5-HT 3 receptor antagonists for obviating chemotherapy-induced emesis [1][2][3]. Azasetron, a potent and specific 5-HT 3 receptor antagonist, was reported to inhibit nausea and vomiting induced by anticancer agents in animals and humans [4][5][6]. It has been reported that the N-oxidation of the azabicyclooctane ring of azasetron (M1) was catalyzed by both the flavin-containing monooxygenases and cytochrome P-450 in rat liver microsomes.…”

Section: Introductionmentioning

confidence: 99%

Simple determination of azasetron in rat plasma by column‐switching high‐performance liquid chromatography

Um¹,

Chae²,

Park³

et al. 2010

J of Separation Science

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For the quantification of azasetron in rat plasma samples, a column-switching HPLC method was developed and validated. Following dilution of plasma samples with mobile phase A (17 mM potassium phosphate buffer (pH 3.0)) and simple protein precipitation by addition of perchloric acid (60%), the mixture was directly injected onto the pre-column. After endogenous plasma substances were eluted to waste, the analyte was transferred to the trap column by switching the system. Then, the analyte was back-flushed to the analytical column for separation with mobile phase B (a 22:78 v/v mixture of acetonitrile and 17 mM potassium phosphate buffer (pH 3.0)) and detected at 250 nm using a photodiode array detector. A linear standard curve was obtained in the concentration range of 10-800 ng/mL with the correlation coefficient (r) of 0.9998. The intra- and inter-day precision and accuracy values for azasetron were in the ranges of 0.3-12.9% and 89.7-101.4%, respectively. The method was valid in terms of specificity, precision, and accuracy. In addition, this efficient analytical method was successfully applied to determine plasma concentrations of azasetron following oral administration of azasetron at a dose of 4.0 mg/kg to rats.

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Clinical Evaluation of Antiemetic Effects of 5-hydroxytryptamine Receptor type 3 (5HT<sub>3</sub> Receptor) Antagonists Based on Changes in Eating Condition in Cancer Patients Receiving Chemotherapy

Cited by 2 publications

References 4 publications

Method for Individualized Evaluation of Antiemetic Effect Induced by 5-HT<sub>3</sub> Receptor Antagonist

Method for Individualized Evaluation of Antiemetic Effect Induced by 5-HT<sub>3</sub> Receptor Antagonist

Simple determination of azasetron in rat plasma by column‐switching high‐performance liquid chromatography

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