DP-VPA / D-Pharm, Jiangsu NHWA Pharma - LARVOL DELTA

Population Pharmacokinetics and Exposure-Safety of Lipophilic Conjugates Prodrug DP-VPA in Healthy Chinese Subjects for Dose Regime Exploring. (PubMed, Eur J Pharm Biopharm) - "DP-VPA showed good tolerance after a single dose of 600-2400 mg with nonlinear PK and was affected by dosage and food. Based on the association between neurological ADRs and higher exposure to DP-VPA by exposure-safety analysis, 900-1200 mg was recommended for subsequent study of safety and clinical effectiveness."

Journal • PK/PD data • CNS Disorders • Epilepsy

Lithium bidirectionally regulates depression- and mania-related brain functional alterations without worsening cognitive function in patients with bipolar disorder. (PubMed, Front Psychiatry) - "We enrolled 149 drug-naïve patients with BP; 99 patients experiencing first depressive episodes were allocated randomly to four treatment groups [lithium (DP/Li), lithium with lamotrigine (LTG; DP/Li+LTG), LTG (DP/LTG), and valproate (VPA) with LTG (DP/VPA+LTG)], and 50 experiencing first hypo-manic episodes were allocated to two treatment groups (MA/Li and MA/VPA)...Our results showed that lithium bidirectionally regulates depression- and mania-associated brain functional abnormalities in patients with BP. Lithium monotherapy has a better antimanic effect than VPA, is superior to other tested treatments in improving cognition during the course of BP, and has satisfactory antidepressant effects in patients with BP."

Journal • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

"Another good day in the lab #MDP #ILAM crowding termination at MDP Vpacing @shivkumarmd @DrRoderickTung @drbilalmunir @UCDavisHealth" (@DrSrivatsa)

l-Cysteine decorated nanoscale metal-organic frameworks delivering valproic acid/cisplatin for drug-resistant lung cancer therapy. (PubMed, Chem Commun (Camb)) - "We design multifunctional CDDP-VPA@ZrMOF-Cys-PEG nanoparticles (CVZP NPs) based on the properties of valproic acid (VPA) that can downregulate the expression of vascular endothelial growth factor (VEGF) to reduce the drug resistance of tumor cells. In vivo experiments confirm that chemotherapy combined with microwave thermal therapy (MWTT) can significantly improve the therapeutic effect of cisplatin-resistant lung cancer."

Journal • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Valproic Acid Decreases Resuscitation Requirements After Hemorrhage in a Prolonged Damage Control Resuscitation Model. (PubMed, J Trauma Acute Care Surg) - "Addition of a single dose of VPA significantly decreases the volume of resuscitation required in a p-DCR model."

Journal • Hematological Disorders • Mood Disorders

Polymorphs of DP-VPA solid solutions and their physicochemical properties. (PubMed, J Pharm Sci) - "Further analysis revealed that Form A transforms into Form B through milling. Given the physicochemical properties of the available physical forms, Form B may be the optimal form for the formulation and development of antiepileptic drugs."

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Determination of DP-VPA and its active metabolite, VPA, in human plasma, urine, and feces by UPLC-MS/MS: a clinical pharmacokinetics and excretion study. (PubMed, Drug Test Anal) - "The intra- and inter-batch coefficients of variation in three matrices ranged from 1.7% to 12.4% while the accuracy values ranged from 85.4% to 111.7%. The developed methods were successfully applied to determine pharmacokinetics of DP-VPA tablet after a single oral dose of 1200 mg in 12 healthy Chinese subjects under fed condition."

Clinical • Journal • PK/PD data

Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity-An Isobolographic Analysis. (PubMed, Int J Mol Sci) - "The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)-valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. The combination of CDDP/SAHA and CDDP/VPA in the MDA-MB-231 triple negative breast cancer (TNBC) cells with increased activity of Notch1, as well as CDDP/VPA in the MDA-MB-231 cells with decreased activity of Notch1, yielded an additive interaction, whereas additivity with a tendency towards antagonism was observed for the combination of CDDP/SAHA in MDA-MB-231 cells with the decreased activity of Notch1. Our studies demonstrated that SAHA and VPA might be considered as potential therapeutic agents in combination therapy with CDDP against TNBC with altered Notch1 activity."

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