The influence of piperine on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy volunteers

Abstract

Purpose

Piperine (PIP) has been found to inhibit P-glycoprotein (P-gp) function in rats, suggesting that it may have the potential to modulate P-gp-mediated drug efflux in humans. The aim of this study was to evaluate the effect of PIP on the pharmacokinetics of fexofenadine (FEX), a P-gp substrate, in healthy volunteers.

Methods

An open-label, two-period, sequential study involving 12 healthy volunteers was conducted. A single oral dose of FEX 120 mg was given to volunteers during the control phase and after the treatment phase. A once-daily oral dose of PIP 20 mg was given to volunteers during the treatment phase (10 days). Blood samples were collected at predefined time intervals, and plasma samples containing FEX were analyzed by liquid chromatography-tandem mass spectrometry.

Results

Treatment with PIP significantly increased maximum plasma concentration of FEX [406.9 (control) vs. 767 ng/mL (treatment)] and area under the plasma concentration–time curve [3403.7 (control) vs. 5724.7 ng.h/mL (treatment)] when compared to the control phase. In contrast, PIP treatment significantly decreased apparent oral clearance of FEX [35.4 (control) vs. 20.7 L/h (treatment)] as compared to the control. There was no significant change observed in the half life and renal clearance of FEX between the treatment phase and control phase.

Conclusions

The results suggest that altered pharmacokinetics and enhanced bioavailability of FEX might be attributed to PIP-mediated inhibition of P-gp drug efflux. Therefore, intake of PIP or dietary supplements containing PIP may potentially enhance the absorption or bioavailability of P-gp substrate drugs in addition to FEX.

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Female Reproductive Parameters in Wild Geladas ( Theropithecus gelada )

Abstract

Accurate data on reproductive parameters are essential for evaluating the adaptive and mechanistic bases of variation within and between species. Here, we combine fecal ovarian hormone analysis with measurements of sex skin swellings and reproductive behavior to describe female reproduction in geladas living in the Simien Mountains National Park, Ethiopia. We collected 10 years of reproductive data from 197 females across 36 units, with hormone data from a subset of these females (60 females from 16 units). First, we use these data to calculate age at maturation, age at first birth, interbirth interval, menstrual cycle length, gestation length, and duration of postpartum amenorrhea. Second, we present composite profiles of ovarian hormones, i.e., estrogens, progestogens, and sex skin measures across reproductive stages. Third, we examine whether ovarian hormones, sex skin phenotypes, and/or reproductive behaviors reliably reflect fertility or pregnancy in female geladas. The reproductive parameters calculated from our data were similar to those in previous studies on geladas and within the range of those for closely-related baboon species. We were able to reliably identify fertility and pregnancy using fecal estrogens only. The tumescent sex skin phenotypes and reproductive behaviors associated with fertility were also observed across all reproductive stages. We suggest that their presence outside of fertility may be a by-product of the flexibility needed for one or more female counterstrategies to infanticide.

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Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus

Abstract

Introduction

Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients.

Methods

Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days. Blood and urine samples were collected at predetermined time points. The primary endpoint was evaluation of correlations between changes from baseline in urine volume and factors that are known to affect urine volume and between actual urine volume and these factors.

Results

Canagliflozin transiently increased urine volume and urinary sodium excretion on Day 1 with a return to baseline levels thereafter. Canagliflozin administration increased urinary glucose excretion, which was sustained during repeated-dose administration. Plasma atrial natriuretic peptide (ANP) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels decreased, while plasma renin activity increased. On Day 1 of treatment, changes in sodium and potassium excretion were closely correlated with changes in urine output. A post hoc multiple regression analysis showed changes in sodium excretion and water intake as factors that affected urine volume change at Day 1. Furthermore, relative to that at baseline, canagliflozin decreased blood glucose throughout the day and increased plasma total GLP-1 after breakfast.

Conclusion

Canagliflozin induced transient sodium excretion and did not induce water intake at Day 1; hence, natriuresis rather than glucose-induced osmotic diuresis may be a major factor involved in the canagliflozin-induced transient increase in urine output. In addition, canagliflozin decreased plasma ANP and NT-proBNP levels and increased plasma renin activity, which may be a compensatory mechanism for sodium retention, leading to subsequent urine output recovery.

Clinical trial registration

UMIN000019462.

Funding

Mitsubishi Tanabe Pharma Corporation.

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A Review of Clinical Practice Guidelines for the Management of Hypertriglyceridemia: A Focus on High Dose Omega-3 Fatty Acids

Abstract

Cardiovascular (CV) disease remains the leading cause of preventable death in the US. Hyperlipidemia is a major modifiable risk factor for CV disease, and after numerous clinical trials have demonstrated that reductions in low-density lipoprotein (LDL) cholesterol with statin therapy can prevent major adverse CV events, statins have emerged as the drug of choice to lower LDL cholesterol and reduce CV risk. However, some statin-treated patients remain at high residual risk of CV events despite achieving low LDL cholesterol levels, especially if their triglyceride (TG) levels are elevated or their high-density lipoprotein (HDL) cholesterol levels low. Evidence from genetic and observational studies has linked elevated TG levels to an increased risk of CV events. Furthermore, very high TG levels are associated with acute pancreatitis. Consequently, several clinical practice guidelines provide recommendations for the management and treatment of high and very high TG levels. This review focuses on the clinical practice guidelines for the management of hypertriglyceridemia and the role of prescription omega-3 fatty acids in preventing pancreatitis and CV disease in individuals with high and very high TG levels.

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Chronic Obstructive Pulmonary Disease Individualized Therapy: Tailored Approach to Symptom Management

Abstract

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality. COPD is typified by persistent, progressive airflow limitation and a range of respiratory and systemic symptoms such as breathlessness, coughing, wheezing, depression, anxiety, general fatigue, and sleeping difficulties. Despite receiving treatment for COPD, many patients suffer from regular symptoms that affect their daily lives and lead to increased morbidity. These symptoms vary in severity, frequency, and type, and can occur at any time throughout the 24-h day, with over half of patients with COPD experiencing symptoms in the morning, during the day, and at nighttime. Despite the prevalence of symptoms, patient and physician perception of the impact of COPD symptoms on patients' lives is not always in concordance. Dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and long-acting beta agonist (LABA) has the potential to treat the symptoms of COPD in addition to improving lung function. This review therefore examines the burden of symptoms experienced throughout the day by patients with COPD and the evidence for combined LAMA/LABA treatment in terms of symptom management. As patients with COPD experience varying symptoms throughout the course of their disease, the role of tailoring treatment to the individual needs of the patient is also examined. We conclude that the symptoms of COPD are troublesome, variable, can occur during all parts of the 24-h day, and have a substantial impact on patients' health status and quality of life. In order to provide effective, patient-orientated care, patients with COPD should be evaluated on the basis of lung function, the frequency of symptoms, and patient-perceived impact of symptoms on their lives. Therapy should be chosen carefully based on individualized assessment, ensuring personalization to the individual needs of the patient.

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The risk of postoperative bleeding – A (DErmatoSurgical Study Initiative) DESSI-Study

	If a surgical procedure in patients on a combination therapy of 2 or more antiplatelet cannot be postponed, it should be conducted with the patient remaining on combination therapy.		Alexandros G. Sfakianakis
	Discontinuation of phenprocoumon therapy and subsequent switching to low-molecular-weight heparin was associated with the highest risk of bleeding (9.26%).		Alexandros G. Sfakianakis
	Platelet inhibitors should not be stopped prior to surgery		Alexandros G. Sfakianakis
	Discontinuation of Direct Oral Anticoagulants (DOACs) is recommended 24 hours prior to surgery.		Alexandros G. Sfakianakis
	The risk of postoperative bleeding		Alexandros G. Sfakianakis

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Inflammationsmarker in der Identifikation von infektiösen Komplikationen in der Kolorektalchirurgie

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