Pharmacokinetic interaction of single dose of piperine with steady‐state carbamazepine in epilepsy patients

Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability‐enhancer. The present study aimed at evaluating the effect of piperine on the steady‐state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t‐test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC_0‐12hr (p < 0.001), average C_ss (p < 0.001), t_1\2el (p < 0.05) and a decrease in K_el (p < 0.05), in both the dose groups, whereas changes in K_a and t_1\2a were not significant. Cmax (p < 0.01) and t_max (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption. Copyright © 2009 John Wiley & Sons, Ltd.     

An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation

A T helper cell type 1–mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RB^high CD4⁺ T cells and can be prevented by cotransfer of the CD45RB^low subset. The immune-suppressive activities of the CD45RB^low T cell population can be reversed in vivo by administration of an anti-transforming growth factor β antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RB^low population. This population isolated from IL-10–deficient (IL-10^−/−) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti–murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RB^low CD4⁺ cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RB^high CD4⁺ cells, as CD45RB^low CD4⁺ cells from WT mice were able to inhibit colitis induced by IL-10^−/− CD45RB^high CD4⁺ cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.     

Clinical Validation of Global Coagulation Tests to Guide Blood Component Transfusions in Cirrhosis and ACLF

Background and AimsPatients with cirrhosis and acute-on-chronic liver failure (ACLF) may have bleeding complications and need for invasive procedures. Point-of-care (POC) coagulation tests like thromboelastography (TEG) and Sonoclot may be better for guiding patient management than the standard coagulation tests (SCTs), like prothrombin time, platelet count and international normalized ratio.MethodsWe prospectively compared and validated the POC tests and SCTs in 70 persons with ACLF and 72 persons with decompensated cirrhosis who had clinical bleeding and checked for episodes of re-bleeding and transfusion requirements. We assessed pre-procedure requirement of blood components when correction was done based on an SCT or POC strategy.ResultsEpisodes of bleeding were seen in 45% and 28% of ACLF and cirrhosis patient, respectively (p=0.036), with the major site of bleeding being gastrointestinal (31% and 16%, respectively). Platelet counts correlated with TEG-maximum amplitude in cirrhosis (p=0.045) and prothrombin time correlated positively with TEG-reaction (R) time (p=0.032), TEG-Clot kinetics (K) time (p=0.042), Son-activated clotting time (p=0.038) and negatively with clot rate (p=0.043) in ACLF, making these correctable target variables in POC transfusion algorithms. Of 223 procedures, transfusion of fresh frozen plasma and platelet concentrate was reduced by 25% (p=0.035) and 20.8% (p=0.045) by using a POC strategy in 76 patients. Correction of deranged Son-activated clotting time and TEG-reaction time was noted in 68% and 72% after 24 h of fresh frozen plasma transfusion in ACLF and 85% and 80% in cirrhosis, respectively.ConclusionsOur study clinically validates that POC tests can better detect coagulation defects and transfusion thresholds in ACLF and cirrhosis, whereas use of conventional tests appear to be less suitable in patients with clinical bleeding.Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT04332484","term_id":"NCT04332484"}}NCT04332484.