Predicting Resolvin D1 Pharmacokinetics in Humans with Physiologically-Based Pharmacokinetic Modeling.

Sjögren's syndrome (SS) is an autoimmune disease with no effective treatment options. Resolvin D1 (RvD1) belongs to a class of lipid-based specialized pro-resolving mediators that showed efficacy in preclinical models of SS. We developed a physiologically-based pharmacokinetic (PBPK) model of RvD1 in mice and optimized the model using plasma and salivary gland pharmacokinetic (PK) studies performed in NOD/ShiLtJ mice with SS-like features. The predictive performance of the PBPK model was also evaluated with two external datasets from the literature reporting RvD1 PKs. The PBPK model adequately captured the observed concentrations of RvD1 administered at different doses and in different species. The PKs of RvD1 in virtual humans were predicted using the verified PBPK model at various doses (0.01-10 mg/kg). The first-in-human predictions of RvD1 will be useful for the clinical trial design and translation of RvD1 as an effective treatment strategy for SS.

Herbal medicines: challenges in the modern world. Part 4. Canada and United States.

INTRODUCTION: Similar to other nations North American people used herbs for thousands of years to treat diseases and purify their spirits. By the middle of the 1900s, evidence-based conventional medicine received wide acceptance in Canada and the United States (US). Nowadays, people are going back to their roots and actively using herbal medicines (HMs) and natural health products (NHPs). Areas covered: This article is focusing on use and regulation of the HMs and NHPs in Canada and the US, raises concerns regarding HM and NHP safety and efficacy, offers suggestions on how to overcome these problems. Materials available from legislative and governmental websites, PubMed and news media were used. Expert commentary: Use of HMs, especially dietary supplements is widespread among adults in Canada and US. HMs and NHPs are regulated in both countries, but minimum criteria for product approval and post-market surveillance have been set. Concerns of quality, contamination, adulteration, and efficacy in are of central importance in the discussion of HMs and NHPs. Detailed product description and research are of vital importance to ensure safety and efficacy of these products. Additionally, 'herbal' education of healthcare providers and patients is needed to guarantee further successful integration of HM and conventional medicines.

Pharmacodynamic studies of voriconazole: informing the clinical management of invasive fungal infections.

INTRODUCTION: Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections (IFI), including aspergillosis, candidiasis, Scedosporium infection, and Fusarium infection. IFI often occur in immunocompromised patients, leading to increased morbidity and mortality. AREAS COVERED: The objective of this review is to summarize the pharmacodynamic properties of voriconazole and to provide considerations for potential optimal dosing strategies. Studies have demonstrated superior clinical response when an AUC/MIC >25 or Cmin/MIC >1 is attained in adult patients, correlating to a trough concentration range as narrow as 2-4.5 mg/L; however, these targets are poorly established in the pediatric population. Topics in this discussion include voriconazole use in multiple age groups, predisposing patient factors for IFI, and considerations for clinicians managing IFI. Expert commentary: The relationship between voriconazole dosing and exposure is not well defined due to the large inter- and intra-subject variability. Development of comprehensive decision support tools for individualizing dosing, particularly in children who require higher dosing, will help to increase the probability of achieving therapeutic efficacy and decrease sub-therapeutic dosing and adverse events.