Receptor occupancy theory-based analysis of interindividual differences in antiemetic effects of 5-HT3 receptor antagonists

Ayuhara, Hideaki; Takayanagi, Risa; Okuyama, Kiyoshi; Yoshimoto, Koichi; Ozeki, Takeshi; Yokoyama, Hiroyuki; Yamada, Yasuhiko

doi:10.1007/s10147-009-0912-5

Cited by 11 publications

(11 citation statements)

References 15 publications

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“…Among these articles, for benzodiazepines, dopamine D 2 antagonists, dopamine D 2 agonists, and histamine H 1 antagonists, we reported that theoretical calculated values reflected the actual values measured by Positron Emission Tomography (PET) [ 10 , 31 - 34 ]. Also, with regard to other drugs, we suggested that it was possible to analyze the effects of drugs by using theoretical calculated values [ 4 - 7 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…We have been studying the receptor occupancy, which integrates pharmacokinetic and pharmacodynamics data, of a variety of drugs that exert pharmacological effects through receptors, and theoretically evaluated clinical and adverse effects by retrospective analysis [ 4 - 7 ]. Our findings for sumatriptan indicate that receptor binding occupancy could be a useful parameter for clinical evaluation irrespective of the administered form [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Theory-based analysis of clinical efficacy of triptans using receptor occupancy

et al. 2014

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BackgroundTriptans, serotonin 5-HT1B/1D receptor agonists, exert their action by targeting serotonin 5-HT1B/1D receptors, are used for treatment of migraine attack. Presently, 5 different triptans, namely sumatriptan, zolmitriptan, eletriptan, rizatriptan, and naratriptan, are marketed in Japan. In the present study, we retrospectively analyzed the relationships of clinical efficacy (headache relief) in Japanese and 5-HT1B/1D receptor occupancy (Φ1B and Φ1D). Receptor occupancies were calculated from both the pharmacokinetic and pharmacodynamic data of triptans.MethodsTo evaluate the total amount of exposure to drug, we calculated the area under the plasma concentration-time curve (AUCcp) and the areas under the time curves for Ф1B and Ф1D (AUCФ1B and AUCФ1D). Moreover, parameters expressing drug transfer and binding rates (A cp , A Ф 1B , A Ф 1D ) were calculated.ResultsOur calculations showed that Фmax1B and Фmax1D were relatively high at 32.0-89.4% and 68.4-96.2%, respectively, suggesting that it is likely that a high occupancy is necessary to attain the clinical effect. In addition, the relationships between therapeutic effect and AUCcp, AUCΦ1B, AUCΦ1D, and A cp · AUCcp differed with each drug and administered form, whereas a significant relationship was found between the therapeutic effect and A Φ 1B · AUCΦ1B or A Φ 1D · AUCΦ1D that was not affected by the drug and the form of administration.ConclusionsThese results suggest that receptor occupancy can be used as a parameter for a common index to evaluate the therapeutic effect. We considered that the present findings provide useful information to support the proper use of triptans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Theory-based analysis of clinical efficacy of triptans using receptor occupancy

et al. 2014

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“…Also, the active metabolite M1 maintains high receptor occupancy and prolongs action duration [8]. Ayuhara et al [10] reported that the occupancy of the 5-HT 3 receptor correlated with the clinical efficacy of 5-HT 3 receptor antagonists.…”

Section: Discussionmentioning

confidence: 99%

“…Many clinical studies have compared ramosetron at 0.3 mg with ondansetron between 4-16 mg [11-13,16,17]. Previous pharmacokinetic studies used ramosetron at 0.3 mg and ondansetron at 4 mg [9,10]. Ondansetron is known not to have a linear dose response curve.…”

Section: Discussionmentioning

confidence: 99%

Comparison of ramosetron's and ondansetron's preventive anti-emetic effects in highly susceptible patients undergoing abdominal hysterectomy

Lee

Park

Choi

et al. 2011

Korean J Anesthesiol

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BackgroundThis study compared the preventive effects of ramosetron and ondansetron on postoperative nausea and vomiting (PONV) in highly susceptible patients undergoing abdominal hysterectomy.MethodsIn a prospective, randomized, double-blinded study, a total of 120 highly susceptible women (nonsmokers, those receiving opioid-based IV patient-controlled analgesia [PCA]) undergoing abdominal hysterectomy were included in the study. Patients were divided into 2 groups and each group received either 0.3 mg of ramosetron or 4 mg of ondansetron, IV. All patients received fentanyl-based IV PCA during the 48 h postoperative periods. The incidences of PONV and side effects of 5-HT3 antagonists (headache and dizziness) were assessed at 3 intervals (<2 h, 2-24 h and 24-48 h) postoperatively.ResultsPatients in the ramosetron group showed a significantly higher ratio of complete response and lower incidence of nausea during the 24-48 h interval after surgery compared with those the ondansetron group.ConclusionsRamosetron (0.3 mg) is more effective in preventing delayed PONV in highly susceptible women undergoing abdominal hysterectomy compared with ondansetron (4 mg).

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“…Also, the active metabolite M1 maintains high receptor occupancy and prolongs action duration. [29] Ayuhara et al [31] reported that the occupancy of the 5-HT3 receptor correlated with the clinical efficacy of 5-HT3 receptor antagonists. Our study is based on ramosetron and ondansetron.There were no statistically significant differences between the two groups in terms of demographic characteristics of the patients namely age, sex and body weight ( Table 1).…”

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Ramosetron: Prevention for Post Operative Nausea and Vomiting After Laparoscopic Cholecystectomy- A Prospective, Randomized, Double-Blind Comparision With Ondasetron

Das¹,

Majumdar²,

Banerjee³

et al. 2013

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BACKGROUND: Postoperative nausea and vomiting (PONV) frequently hampers implementation of laparoscopic surgery in spite of so many antiemetic drugs and regimens. This study was to compare the efficacy of Ramosetron and Ondansetron in (PONV) after Laparoscopic Cholecystectomy. MATERIALS & METHODS: 124 adult patients of either sex, of ASA physical status I and II, scheduled for Laparoscopic Cholecystectomy operation, were randomly allocated into Group A (n=62) patients received IV Ondansetron 4mg and Group B (n=62) patients received IV Ramosetron (0.3 mg). Drug was administered prior to induction of GA. Episodes of PONV were compared between the groups at 4 hrs,4.5 hrs,5 hrs,5.5 hrs and 6 hrs post-operatively. STATISTICAL ANALYSIS: The raw data analyzed by SPSS Ⓡ Ⓡ Ⓡ Ⓡ statistical package version 18.0 (SPSS Inc., Chicago, IL, USA). Numerical variables were compared by independent sample t test. Chi square test, Officers exact test and Fischer's exact test were used to compare categorical variables between groups. All analysis were two tailed and a P<0.05 was considered statistically significant RESULTS: Statistically significant difference between groups A and B (P <0.05), was found showing that Ramosetron was superior than Ondansetron in antiemetic efficacy and Ramosetron emerged as a better antiemetic than Ondansetron in 1st12 hrs post-operative period. The post-operative mean Visual Analogue Scale( VAS) scoring for the severity of PONV between the two study groups at 4 hrs and 6 hrs post operative period, revealed that there was statistically significant difference between the two groups , showing that severity of nausea was more in case of Ondansetron than Ramosetron. CONCLUSION: So, it was evident that single dose preoperative administration of IV Ramosetron ( 0.3 mg ) has better efficacy than IV Ondansetron ( 4 mg ) in reducing the episodes of PONV over 12 hours postoperative period in patients undergoing Laparoscopic Cholecystectomy under GA. DISCUSSION:The complex act of vomiting involves coordination of the respiratory, gastrointestinal, and abdominal musculature and is controlled by the emetic center. The area situated in the lateral reticular formation close to the tractus solitarius in the brain stem is thought to be the emetic center. [1,2,25] Stimuli from several areas within the central nervous system can affect the emetic center. [1] These include afferents from the pharynx, gastrointestinal tract and mediastinum, as well as afferents from the higher cortical centers (including the visual center and the vestibular portion of the eighth cranial nerve) and the chemoreceptor trigger zone (CTZ) in the area postrema. The area postrema of the brain is rich in dopamine, opioid, and serotonin or 5-hydroxytryptamine (5HT3) receptors. Four major neuro transmitter systems appear to play important roles in mediating the emetic response viz. dopaminergic, histaminic (H1), cholinergic, muscarinic and 5HT3. [1] As there are four different types of receptors, there are at least four sites of action of the antiemeti...

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Receptor occupancy theory-based analysis of interindividual differences in antiemetic effects of 5-HT3 receptor antagonists

Cited by 11 publications

References 15 publications

Theory-based analysis of clinical efficacy of triptans using receptor occupancy

Theory-based analysis of clinical efficacy of triptans using receptor occupancy

Comparison of ramosetron's and ondansetron's preventive anti-emetic effects in highly susceptible patients undergoing abdominal hysterectomy

Ramosetron: Prevention for Post Operative Nausea and Vomiting After Laparoscopic Cholecystectomy- A Prospective, Randomized, Double-Blind Comparision With Ondasetron

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