Drug Des Dev Ther
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Rolapitant is a highly selective neurokinin-1 receptor antagonist, orally administered for a single dose of 180 mg before chemotherapy with granisetron D1, dexamethasone 8 mg BID on day 2-4. It has a unique pharmacological characteristic of a long plasma half-life (between 163 and 183 hours); this long half-life makes a single use sufficient to cover the delayed emesis risk period. No major drug-drug interactions between rolapitant and dexamethasone or other cytochrome P450 inducers or inhibitors were observed. ⋯ The primary endpoint was the proportion of patients achieving a complete response (defined as no emesis or use of rescue medication) in the delayed phase (>24-120 hours after chemotherapy). In comparison to granisetron (10 μg/kg intravenously) and dexamethasone (20 mg orally) on day 1, and dexamethasone (8 mg orally) twice daily on days 2-4 and placebo, rolapitant showed superior efficacy in the control of delayed and overall emesis. This review aims at revising the pharmacological characteristics of rolapitant, offering an updated review of the available clinical efficacy and safety data of rolapitant in different clinical settings, highlighting the place of rolapitant in the management of chemotherapy-induced nausea and vomiting (CINV) among currently available guidelines, and exploring the future directions of CINV management.
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Ischemia-reperfusion (I/R) injury is a common cause of patient morbidity and mortality in the perioperative period. Patients undergoing long-lasting, abdominal, and urogenital surgeries with risk factors such as advanced age, peripheral artery disease, diabetes mellitus, renovascular disease, and congestive heart failure are candidates for acute kidney injury (AKI) due to impaired renal perfusion and decreased functional renal reserve. Pharmacological agents with multiple functions and anti-oxidative and anti-inflammation properties may be promising preventative strategies for AKI. Recently, dexmedetomidine (dex) has been postulated to have renoprotective effects. ⋯ The NGAL levels and histopathological findings reflected protection by dex against renal I/R injury. However, the same exact results could not be mentioned for remifentanil depending on our study results.
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Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML) cells and sensitivity of tyrosine kinase inhibitor in vitro. ⋯ NVP-BEZ235 effectively inhibited cell proliferation by G0/G1 cell cycle arrest and induced apoptosis through deregulating PI3K/Akt/mTOR pathway in CML cells; in addition, NVP-BEZ235 can enhance cell autophagy, and is conducive to raising CML cell sensitivity to imatinib to inhibit the growth of imatinib-resistant cells.
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Review Meta Analysis Comparative Study
Comparison of dexmedetomidine and fentanyl as local anesthetic adjuvants in spinal anesthesia: a systematic review and meta-analysis of randomized controlled trials.
To compare the effects of dexmedetomidine (Dex) and fentanyl as adjuvants to local anesthetics in spinal anesthesia. ⋯ Compared to fentanyl, Dex as local anesthetics adjuvant in spinal anesthesia prolonged the duration of spinal anesthesia, improved postoperative analgesia, reduced the incidence of pruritus, and did not increase the incidence of hypotension and bradycardia.
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Randomized Controlled Trial
A first-in-human, double-blind, placebo-controlled, randomized, dose escalation study of DWP05195, a novel TRPV1 antagonist, in healthy volunteers.
DWP05195 is a transient receptor potential vanilloid 1 (TRPV1) antagonist developed for managing pain. The purpose of this study was to evaluate the pharmacodynamics pharmacokinetics, safety, and tolerability of DWP05195 in healthy subjects. This was a first-in-human randomized, double-blinded, placebo-controlled, dose escalation study. ⋯ The pharmacological activity of DWP05195, measured using HPtr and HPtol, increased as expected in a dose-dependent manner owing to increased systemic exposure, indicating that DWP05195 can be used as a TRPV1 antagonist for pain management.