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BMC Anesthesiology Dec 2023Postoperative nausea and vomiting (PONV) is a common side effect associated with general anesthesia. Both ondansetron and aprepitant been effectively used to prevent... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Postoperative nausea and vomiting (PONV) is a common side effect associated with general anesthesia. Both ondansetron and aprepitant been effectively used to prevent PONV. However, there is a disagreement of opinions regarding the superiority of these two drugs. This study aims to compare the efficacy of aprepitant with ondansetron in preventing PONV following orthognathic surgeries.
METHODS
In this double-blinded clinical trial, 80 patients scheduled for orthognathic surgery at Imam Hossein Hospital, Tehran, Iran, were randomly assigned to two groups. A standardized anesthesia protocol was used for all patients. The first group received a placebo capsule administered one hour before the surgical procedure along with 4 mg (2 ml) of ondansetron intravenously after anesthesia induction. The second group was given 80 mg aprepitant capsules one hour before the surgery, followed by an injection of 2 ml intravenous distilled water after anesthesia induction. The occurrence and severity of PONV, the amount of rescue medication required, and the complete response of patients assessed within 24 h after the surgery.
RESULTS
There were no significant differences in demographic data between the two groups. Patients in the aprepitant group had a significantly lower incidence and severity of nausea (2.5% versus 27.5%), vomiting (5% versus 25%), and required fewer rescue medications (7.5% versus 62.5%) compared to the ondansetron group. Additionally, the aprepitant group showed a higher complete response rate (90% versus 67.5%) in the 0-2 and 12-24 postoperative hours.
CONCLUSION
According to the findings of this study, aprepitant has demonstrated a greater efficacy in preventing PONV following orthognathic surgery, when compared to ondansetron.
TRIAL REGISTRATION
Iranian Registry of Clinical Trials (IRCT code: IRCT20211205053279N3), date of registration: 16/12/2022.
Topics: Humans; Ondansetron; Aprepitant; Postoperative Nausea and Vomiting; Antiemetics; Orthognathic Surgery; Iran; Double-Blind Method
PubMed: 38093201
DOI: 10.1186/s12871-023-02371-y -
ACS Omega Nov 2022This study focused on improving the physicochemical characteristics of aprepitant with poor water solubility by preparing solid dispersion (SD). To prepare the SD with...
This study focused on improving the physicochemical characteristics of aprepitant with poor water solubility by preparing solid dispersion (SD). To prepare the SD with HPMCAS-LF, the solvent evaporation method was applied. Based on dissolution analysis, the dissolution rate of SD increased by five times compared with aprepitant. In addition, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) results suggested the presence of amorphous-form aprepitant inside SD. According to Fourier transform infrared (FTIR) spectroscopy, intermolecular hydrogen bonds were detected between polymer and aprepitant. The Caco-2 cell experiment proved that SD did not lower the transepithelial electrical resistance (TEER) values but improved the permeation amount of aprepitant. Additionally, the SD of aprepitant displayed excellent stability.
PubMed: 36385804
DOI: 10.1021/acsomega.2c04021 -
Clinical Pharmacology in Drug... Jul 2021Fosaprepitant dimeglumine (FD) is a precursor of aprepitant. FD can be metabolized into aprepitant. This randomized, single-center, open, 2-cycle, single-dose, crossover... (Comparative Study)
Comparative Study Randomized Controlled Trial
Fosaprepitant dimeglumine (FD) is a precursor of aprepitant. FD can be metabolized into aprepitant. This randomized, single-center, open, 2-cycle, single-dose, crossover bioequivalence study compared the pharmacokinetics (PK) and safety of intravenously FD of test and reference products in healthy volunteers (HVs). HVs were assigned to the test group or reference group randomly and given FD intravenously. The plasma concentration of FD and aprepitant was measured using liquid chromatography-tandem mass spectrometry. PK parameters were ascertained based on a noncompartmental model. Data for 29 HVs were obtained. The geometric mean and 90% confidence intervals of maximum plasma concentration (C ), area under the concentration-time curve from time 0 to time of last measurable plasma concentration (AUC ), and area from the last datum point to time infinity (AUC ) of test and reference groups were 101.69% (95.06%, 108.77%), 103.52% (99.15%, 108.09%), and 105.58% (99.51%, 112.01%), respectively. These 3 parameters were within the acceptance range of 80.0% to 125.00%, and the test product was bioequivalent to the reference product. The coefficient of variation (CV) of C , AUC , and AUC was 15.14%, 9.67%, and 11.89%, respectively. Intravenously administered FD provided by 2 sponsors achieved bioequivalence. FD values from test and reference products were bioequivalent. All adverse events were mild and serious adverse events absent in HVs. This study indicated that FD may provide a safer alternative to aprepitant for chemotherapy-induced nausea and vomiting.
Topics: Adolescent; Adult; Aged; Antiemetics; Area Under Curve; Asian People; Chromatography, Liquid; Cross-Over Studies; Female; Humans; Male; Middle Aged; Morpholines; Tandem Mass Spectrometry; Therapeutic Equivalency; Young Adult
PubMed: 33277980
DOI: 10.1002/cpdd.892 -
Journal of Pediatric Surgery Jul 2019This multicenter, randomized, partially-blinded phase IIb study evaluated the pharmacokinetics (PK)/pharmacodynamics, safety, and tolerability of aprepitant in pediatric... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/PURPOSE
This multicenter, randomized, partially-blinded phase IIb study evaluated the pharmacokinetics (PK)/pharmacodynamics, safety, and tolerability of aprepitant in pediatric subjects for the prevention of postoperative nausea and vomiting (PONV).
METHODS
Subjects aged birth to 17 years scheduled to undergo surgery and receive general anesthesia with ≥1 risk factor for PONV were randomly assigned to 1 of 3 aprepitant dose regimens (a single oral dose of aprepitant equivalent to adult doses of 10 mg, 40 mg, or 125 mg), or a control regimen of ondansetron before anesthesia. Assessments included PK, safety, and exploratory efficacy (complete response [CR; no emesis, retching, or dry heaves and no rescue therapy within 0-24 h following surgery] and no vomiting [NV; no emesis, retching, or dry heaves within 0-24 h following surgery]).
RESULTS
Of 220 randomized and treated subjects, 119 receiving a single aprepitant dose were sampled for PK analysis and had evaluable aprepitant plasma concentrations. A dose-dependent relationship in exposure (AUC0-8 h and Cmax) was observed. Aprepitant was generally well tolerated, and the CR and NV rates were high (>80%) across treatment groups.
CONCLUSIONS
PK, safety, and preliminary efficacy analyses support further clinical evaluation of aprepitant for PONV prophylaxis in pediatric patients. CLINICALTRIALS.
GOV ID
NCT01732458 LEVEL OF EVIDENCE: Therapeutic, Level I.
Topics: Adolescent; Antiemetics; Aprepitant; Child; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Infant, Newborn; Male; Postoperative Nausea and Vomiting; Treatment Outcome
PubMed: 30381138
DOI: 10.1016/j.jpedsurg.2018.09.006 -
Liver International : Official Journal... Jul 2024Intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis and limited treatment options. Aprepitant, a selective NK-1R antagonist, can inhibit the growth of various...
BACKGROUND
Intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis and limited treatment options. Aprepitant, a selective NK-1R antagonist, can inhibit the growth of various tumours in vitro and in vivo. However, it remains unclear whether aprepitant has cytotoxic effects on iCCA.
METHODS
We measured the expression of SP/NK-1R in clinical samples of iCCA by immunohistochemistry. Then, we detected the cytotoxic effects of aprepitant on iCCA cells via MTT, EdU and colony formation assay. We constructed a subcutaneous xenograft model of BALB/c nude mice by using HCCC-9810 and RBE cell lines to explore the effects of aprepitant in vivo. To elucidate the potential mechanisms, we explored the pro-apoptotic effect of aprepitant by flow cytometric, western blotting, ROS detection and JC-1 staining. Furthermore, we detected the autophagic level of HCCC-9810 and RBE by western blotting, mRFP-eGFP-LC3 adenovirus transfection and electron microscope.
RESULTS
SP/NK-1R is significantly expressed in iCCA. Aprepitant inhibited human iCCA xenograft growth and dose-dependently decreased the viability of RBE and HCCC-9810 cells. Aprepitant-induced mitochondria-dependent apoptosis through ROS/JNK pathway. Additionally, pretreatment with z-VAD-fmk partly reversed the effect of aprepitant on cell viability, while NAC completely attenuated the cytotoxic effects of aprepitant in vitro. Furthermore, we observed the dynamic changes of autophagosome in RBE and HCCC-9810 cells treated with aprepitant.
CONCLUSION
SP/NK-1R signalling is significantly activated in iCCA and promotes the proliferation of iCCA cells. By contrast, aprepitant can induce autophagy and apoptosis in iCCA cells via ROS accumulation and subsequent activation of JNK.
Topics: Aprepitant; Animals; Humans; Autophagy; Apoptosis; Cholangiocarcinoma; Reactive Oxygen Species; Mice, Nude; Mice, Inbred BALB C; Cell Line, Tumor; Bile Duct Neoplasms; Xenograft Model Antitumor Assays; Neurokinin-1 Receptor Antagonists; Mice; Male; Female; Receptors, Neurokinin-1; Middle Aged; Cell Proliferation
PubMed: 38554043
DOI: 10.1111/liv.15904 -
Cancer Medicine Aug 2023Non-inferiority of NEPA (fixed combination of NK receptor antagonist (RA), netupitant, and 5-HT RA, palonosetron) versus an aprepitant regimen was previously shown in a... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Non-inferiority of NEPA (fixed combination of NK receptor antagonist (RA), netupitant, and 5-HT RA, palonosetron) versus an aprepitant regimen was previously shown in a pragmatic study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC). In the MEC group a numerically higher complete response (CR: no emesis, no rescue) rate was seen for NEPA during the overall 0-120 h phase (NEPA 76.1% vs. 63.1% aprepitant). As NEPA exhibits long-lasting efficacy, this study evaluated a prolonged period up to 144 h, beyond the traditional 120 h post-chemotherapy. In this post-hoc analysis we explore the comparative efficacy of NEPA versus the aprepitant regimen in the MEC group up to 144 h, while also assessing the impact of risk factors on CINV prevention.
METHODS
This was a pragmatic, multicenter, randomized, prospective study. Oral NEPA was administered as a single dose on day 1, while aprepitant was given on days 1-3 + ondansetron on day 1; all patients were to receive dexamethasone on days 1-4. Patients were chemotherapy-naïve and receiving MEC, with a subset evaluation of those with a risk factor for developing CINV (i.e., female, male <60 years, male ≥60 years who received carboplatin, or male ≥60 years with anxiety). CR rates were compared during the extended overall (0-144 h) phase.
RESULTS
The MEC group included 211 patients; of these 181 were in the risk factor subset. Significantly higher CR rates were seen for NEPA than aprepitant during the extended overall phase for the total MEC group (NEPA 77.1%, aprepitant 57.8%, p = 0.003) and also in the subset of patients with CINV risk factors (NEPA 73.9%, aprepitant 56.2%, p = 0.012).
CONCLUSION
A single dose of NEPA, administered on day 1 only, was more effective than a 3-day aprepitant regimen in preventing CINV for an extended duration in patients receiving MEC and in those with emetic risk factors.
Topics: Humans; Male; Female; Aprepitant; Antiemetics; Vomiting; Prospective Studies; Isoquinolines; Quinuclidines; Drug Combinations; Nausea; Cyclophosphamide; Anthracyclines; Antineoplastic Agents; Dexamethasone
PubMed: 37537943
DOI: 10.1002/cam4.6121 -
Pharmaceutics Apr 2020This study aimed to improve the solubility and dissolution of aprepitant, a drug with poor aqueous solubility, using a phosphatidylcholine (PC)-based solid dispersion...
This study aimed to improve the solubility and dissolution of aprepitant, a drug with poor aqueous solubility, using a phosphatidylcholine (PC)-based solid dispersion system. When fabricating the PC-based solid dispersion, we employed mesoporous microparticles, as an adsorbent, and disintegrants to improve the sticky nature of PC and dissolution of aprepitant, respectively. The solid dispersions were prepared by a solvent evaporation technique and characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry, and X-ray powder diffraction. The FTIR results showed that aprepitant interacted with the PC carrier by both hydrogen bonds and van der Waals forces that can also be observed in the interaction between aprepitant and polymer carriers. The solid dispersions fabricated with only PC were not sufficient to convert the crystallinity of aprepitant to an amorphous state, whereas the formulations that included adsorbent and disintegrant successfully changed that of aprepitant to an amorphous state. Both the solubility and dissolution of aprepitant were considerably enhanced in the PC-based solid dispersions containing adsorbent and disintegrant compared with those of pure aprepitant and polymer-based solid dispersions. Therefore, these results suggest that our PC-based solid dispersion system is a promising alternative to conventional formulations for poorly water-soluble drugs, such as aprepitant.
PubMed: 32365589
DOI: 10.3390/pharmaceutics12050407 -
Journal of Neuroinflammation Aug 2022Pyroptosis is a programmed cell death mediated by inflammasomes. Previous studies have reported that inhibition of neurokinin receptor 1 (NK1R) exerted neuroprotection...
BACKGROUND
Pyroptosis is a programmed cell death mediated by inflammasomes. Previous studies have reported that inhibition of neurokinin receptor 1 (NK1R) exerted neuroprotection in several neurological diseases. Herein, we have investigated the role of NK1R receptor inhibition using Aprepitant to attenuate NLRC4-dependent neuronal pyroptosis after intracerebral hemorrhage (ICH), as well as the underlying mechanism.
METHODS
A total of 182 CD-1 mice were used. ICH was induced by injection of autologous blood into the right basal ganglia. Aprepitant, a selective antagonist of NK1R, was injected intraperitoneally at 1 h after ICH. To explore the underlying mechanism, NK1R agonist, GR73632, and protein kinase C delta (PKCδ) agonist, phorbol 12-myristate 13-acetate (PMA), were injected intracerebroventricularly at 1 h after ICH induction, and small interfering ribonucleic acid (siRNA) for NLRC4 was administered via intracerebroventricular injection at 48 h before ICH induction, respectively. Neurobehavioral tests, western blot, and immunofluorescence staining were performed.
RESULTS
The expression of endogenous NK1R and NLRC 4 were gradually increased after ICH. NK1R was expressed on neurons. Aprepitant significantly improved the short- and long-term neurobehavioral deficits after ICH, which was accompanied with decreased neuronal pyroptosis, as well as decreased expression of NLRC4, Cleaved-caspase-1, GSDMD (gasdermin D), IL-1β, and IL-18. Activation of NK1R or PKCδ abolished these neuroprotective effects of Aprepitant after ICH. Similarly, knocking down NLRC4 using siRNA produced similar neuroprotective effects.
CONCLUSION
Aprepitant suppressed NLRC4-dependent neuronal pyroptosis and improved neurological function, possibly mediated by inhibition of NK1R/PKCδ signaling pathways after ICH. The NK1R may be a promising therapeutic target for the treatment of ICH.
Topics: Animals; Aprepitant; Cerebral Hemorrhage; Disease Models, Animal; Mice; Neurons; Neuroprotective Agents; Pyroptosis; RNA, Small Interfering
PubMed: 35922848
DOI: 10.1186/s12974-022-02558-z -
Cancer Nov 2022Pruritus is one of the most common and challenging side effects of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and has impaired patients'... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pruritus is one of the most common and challenging side effects of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and has impaired patients' quality of life and treatment compliance. Our study evaluated the efficacy and safety of aprepitant in managing EGFR-TKIs-related pruritus.
METHODS
This randomized, double-blind, placebo-controlled study was conducted between December 2016 and August 2020 in China. Patients were eligible if they were 18 years or older and had histologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) with first onset of moderate to severe pruritus during EGFR-TKI treatment.
RESULTS
A total of 130 eligible patients were randomly assigned to aprepitant (n = 65) or desloratadine (n = 65) groups. The median (interquartile range [Q1, Q3]) age was 63 (54, 70) years, and 79 (60.8%) were women. Mean visual analog scale scores at baseline were 6.35 (95% confidence interval [CI], 5.89-6.82) in the aprepitant group and 5.94 (95% CI, 5.56-6.32) in the desloratadine group. After 1 week of treatment, 33 (53.2%) patients responded to aprepitant, which was significantly higher than that of 14 (23.7%) patients responded to desloratadine (p = .001). Moreover, patients in the aprepitant group had a significantly shorter response time than patients in the desloratadine group (mean [days], 13.39 [95% CI, 11.08-15.70] vs. 16.67 [95% CI, 14.19-19.13], p = .04). The most frequent drug-related adverse events in aprepitant group and desloratadine were constipation and dry mouth, and all adverse events were grade 1-2.
CONCLUSIONS
To the authors' knowledge, this is the first study to prospectively present that aprepitant elicited a better and faster response and mild toxicity for managing EGFR-TKI induced pruritus than desloratadine.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02646020.
Topics: Female; Humans; Male; Aprepitant; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Lung Neoplasms; Protein Kinase Inhibitors; Pruritus; Quality of Life; Middle Aged; Aged
PubMed: 36197287
DOI: 10.1002/cncr.34474 -
Annals of Hematology Jun 2022Aprepitant (Apr) is an effective antiemetic agent for chemotherapy-induced nausea and vomiting (CINV). Current CINV guidelines recommend the antiemetic combination of a...
Aprepitant (Apr) is an effective antiemetic agent for chemotherapy-induced nausea and vomiting (CINV). Current CINV guidelines recommend the antiemetic combination of a 5-HT3 receptor antagonist, Apr, and dexamethasone (Dex) for highly emetogenic chemotherapies. Apr inhibits CYP3A4 dose-dependently. Since Dex is metabolized by CYP3A4, the combined use of Apr and Dex inhibits Dex metabolism. CINV guidelines therefore recommend dose-reduction of Dex when Apr and Dex are used together. However, there is some controversy over whether or not Dex should be reduced when administered as an antitumor agent for lymphoid malignancies. We retrospectively compared the antitumor effect of Dex-containing chemotherapy in which Dex is administered at the usual dose without Apr (group A) or administered at a half-dose in combination with Apr (group B). We analyzed 62 consecutive patients with refractory or relapsed CD20 + B cell lymphoma who received R-DHAP therapy in our hospital, including 29 and 33 cases in groups A and B, respectively. The response rate at the end of the first course of R-DHAP was 62.1% and 54.5%, respectively (P = 0.61). As another endpoint to evaluate the effect of Dex, group B tended to show greater suppression of the lymphocyte count (P = 0.05). Therefore, decreasing the dose of Dex by half appeared to be reasonable when combined with Apr.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cytochrome P-450 CYP3A; Dexamethasone; Humans; Lymphoma; Nausea; Retrospective Studies; Vomiting
PubMed: 35403851
DOI: 10.1007/s00277-022-04832-9