Evaluation of potential antidiabetic activity of abelmoschus esculentus and evidence of possible pharmacokinetic interaction with metformin

The study is aimed at the evaluation of potential activity of and possible interaction with metformin in animal Models of Diabetes Mellitus. Study objectives include study the anti-diabetic effect of for Diabetes Mellitus in animal models and also to study the effect of Abelmoschus esculentus with metformin and explore any interaction. Plant material was collected () followed by extraction of plant materials () Exudate collection of and activity test study was done (acute toxicity study, according to standard OECD guidelines) Experimental animals were divided into groups. Dosing was done for 28 days. Biochemical parameters were studied. Histopathology studies are done. Results showed that in this study administrations of Abelmoschus esculentus extract (2000mg/kg body weight) Metformin with extract (5mg/kg b.w. and 2000mg/kg body weight and Metformin 5mg/kg body weight decreased elevated blood glucose levels significantly from first to fourth week compared to diabetic control rats and showed minimal safety concerns.

A phase 1 study to assess potential interaction between ASP8062 and alcohol in healthy adult subjects

Background: ASP8062 is a novel orally active GABAB receptor positive allosteric modulator in clinical development for the treatment of alcohol use disorder (AUD) and opioid use disorder (OUD). Aims: This study assessed the potential pharmacokinetic/pharmacodynamic interaction between ASP8062 and alcohol under single-dose conditions in healthy adults. Methods: A double-blind, placebo-controlled, crossover phase 1 study was conducted in which 20 subjects were randomly assigned to four treatment sequences (ASP8062 + alcohol; ASP8062 + placebo alcohol; placebo + alcohol; placebo + placebo alcohol) each consisting of four treatment periods, separated by washout periods of at least 14 days. An analysis of variance was used to assess pharmacokinetic interaction and a mixed-effects analysis of covariance was used to assess pharmacodynamic interaction. Results/outcomes: After administration of alcohol, a mild to minimal increase in plasma exposure (AUCinf and Cmax) of ASP8062 was observed, but tmax and t½ for ASP8062 remained unchanged after administration of alcohol. In contrast, ASP8062 did not affect the AUClast and Cmax of ethanol. No clinically relevant differences in cognition measurements were observed with ASP8062 compared with placebo, but there were expected impairments in psychomotor and executive function with alcohol alone. ASP8062 in combination with alcohol resulted in worse scores in cognition measurements than alcohol alone, but this potentiation was not consistent. ASP8062 administered alone was safe and well-tolerated and safety findings in subjects administered alcohol alone were not augmented when ASP8062 was administered in combination with alcohol. Conclusion/interpretation: The data support further clinical studies investigating ASP8062 in patients with AUD.

LC–MS/MS bioanalytical method for quantification of binimetinib and venetoclax, and their pharmacokinetic interaction

Aim: Because of several prospective benefits, binimetinib (BMT)-venetoclax (VTC) combination can be a better therapeutic strategy to treat cancer. Results: An LC–MS/MS method for simultaneous quantification of BMT and VTC in rat plasma has been developed and validated. Specificity, accuracy, precision and stability results met the acceptance criteria for validation. Accuracy and precisions at all quality control levels were <15%. The study revealed that co-administration of BMT and VTC has no significant effect on their pharmacokinetics. Conclusion: The developed method can provide accurate results for quantification of BMT and VTC over the range of 5–500 ng/ml. The reported pharmacokinetic interaction study results will be useful for future consideration of the combined treatment of BMT and VTC in anticancer chemotherapy regimens.

Effects of concurrent and staggered dosing of semi-solid enteral nutrients on pharmacokinetic behavior of antiepileptic drugs after oral administration in rats

Background The use of enteral nutrients plays a highly important role in accurate nutrition management, but limited information is currently available on the cautionary points of semi-solid enteral nutrients. Aim In this study, we examined whether the pharmacokinetic profiles of sodium valproate (SVA), levetiracetam (LEV), and carbamazepine (CBZ) are affected by altering the dosing time of RACOL®-NF Semi Solid for Enteral Use (RASS), a prescribed semi-solid formula. We also investigated whether the pharmacokinetic interaction observed in this study can be avoided by staggered dosing of the chemical drug and semi-solid enteral nutrient. Methods The plasma concentration of SVA, LEV and CBZ after oral administration was measured by LC-MS/MS method. Results There was no difference in pharmacokinetic characteristics of SVA and LEV when the dosing time of RASS was altered. On the other hand, the plasma concentration of CBZ after oral administration at all sampling points decreased with the extension of the dosing time of RASS, which was consistent with the Cmax and AUC. However, no significant difference was observed in the pharmacokinetic profiles or parameters of CBZ between the short-term and long-term RASS dosing groups by prolonging the administered interval of CBZ and RASS for 2 hr. Conclusion We concluded that the pharmacokinetic profiles of CBZ, but not SVA and LEV, after its oral administration are affected by the dosing time of RASS, but staggered administration of CBZ and RASS prevented their interaction.

A comprehensive review of pharmacokinetic and pharmacodynamic in animals: exploration of interaction with antibiotics of Shuang-Huang-Lian preparations

: As a traditional Chinese medicine, Shuang-Huang-Lian (SHL) has been widely used for treating infectious diseases of the respiratory tract such as encephalitis, pneumonia and asthma. During the past few decades, considerable research has focused on the pharmacological action, pharmacokinetic interaction with antibiotics and clinical applications of SHL. A huge and more recent body of pharmacokinetic study supports the combination of SHL and antibiotics has different effects such as antagonism and synergism. SHL has been one of the best-selling traditional Chinese medicine (TCM) products. However, there is no system review of SHL preparations, ranging from protection against respiratory tract infections to interaction with antibiotics. Since their important significance in clinical therapy, the pharmacodynamic, pharmacokinetic, and interactions with antibiotics of SHL were reviewed and discussed. In addition, this review attempts to explore the possible potential mechanism of SHL preparations in prevention and treatment of COVID-19. We are concerned about what is known of the effects of SHL against virus, bacterium, and its interactions with antibiotics, providing a new strategy for expanding the clinical research and medication of SHL preparations.