SAR247799 is a selective G-protein-biased sphingosine-1 phosphate receptor-1 (S1P1 ) agonist with potential to restore endothelial function in vascular pathologies. SAR247799, a first-in-class molecule differentiated from previous S1P1 -desensitizing molecules developed for multiple sclerosis, can activate S1P1 without desensitization and consequent lymphopenia. The aim was to characterize SAR247799 for its safety, tolerability, pharmacokinetics and pharmacodynamics (activation and desensitization).

Selexipag is a prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension. Cytochrome P450 (CYP) 2C8 is involved in the metabolism of selexipag and its active metabolite, ACT-333679. This study evaluated the interaction of selexipag and clopidogrel, a CYP2C8 inhibitor.

The aim of this study was to characterize the pharmacokinetic/pharmacodynamic relationships of cortisol and the adrenal biomarkers 17-hydroxyprogesterone and androstenedione in children with congenital adrenal hyperplasia (CAH).

The deployment of artesunate for severe malaria and the artemisinin combination therapies (ACTs) for uncomplicated malaria has been a major advance in antimalarial therapeutics. These drugs have reduced treated mortality, accelerated recovery and reduced treatment failure rates and transmission from the treated infection. Artemisinin derivatives remain highly effective against falciparum malaria in most malaria endemic areas, but significant resistance has emerged in the Greater Mekong subregion of Southeast Asia. Resistance to artemisinins was followed by resistance to the ACT partner drugs, and fit multidrug resistant parasite lineages have now spread widely across the region. ACTs remain highly effective against P. vivax and the other malaria species. Recent studies have shown that radical curative regimens of primaquine (to prevent relapse) can be shortened to 7 days, and that the newly introduced single dose tafenoquine is an alternative, although the currently recommended dose is insufficient in Southeast Asia and Oceania. Targeted malaria elimination using focal mass treatments with dihydroartemisinin-piperaquine have proved safe and effective malaria elimination accelerators, but progress overall towards malaria elimination is slow. Indeed since 2015 overall malaria case numbers globally have risen. As new drugs will not become widely available in the near future, active measures to preserve the current antimalarials should be given the highest priority.

The Systematic Tool to Reduce Inappropriate Prescribing is a method to assess patient's medication and has been incorporated into a clinical decision support system: STRIP Assistant. Our aim was to evaluate the effect of recommendations generated using STRIP Assistant on appropriate prescribing and mortality in a preoperative setting.

Patients with metastatic gastrointestinal stromal tumours (GIST) are treated in first line with the oral tyrosine kinase inhibitor, imatinib, until progressive disease. With this fixed dosing regimen, only approximately 40% of patients reach adequate plasma levels within the therapeutic index. Therapeutic drug monitoring (TDM) is a solution to reach plasma levels within the therapeutic index. However, introducing TDM will also increase costs, due to prolonged imatinib use and laboratory costs. The aim of this study was to evaluate the cost-effectiveness of TDM in patients with metastatic/unresectable GIST treated with imatinib as a first line treatment, compared with fixed dosing.

To externally validate an earlier characterized relationship between bedaquiline exposure and decline in bacterial load in a more difficult-to-treat patient population, and to explore the performances of alternative dosing regimens through simulations.

Antihistamines make up the first line of treatments against motion-sickness. Still, their efficacy and specific mechanism have come into question. The aim of this study was to investigate the effect of meclizine on motion-sensitivity.

In X-linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X-linked hypohidrotic ectodermal dysplasia patients may lead to life-threatening hyperthermia, especially during hot weather or febrile illness. Fc-EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc-EDA and efficacy if applied prenatally. Anti-drug antibodies were detected after intravenous administration in adult males and nonpregnant females, but not in pregnant women when Fc-EDA was delivered intra-amniotically. Most importantly, there was no detectable immune response to the investigational drug in neonates treated by intravenous infusions and in infants who had received Fc-EDA in utero. In conclusion, the safety profile of this drug encourages further development of prenatal EDA1 replacement therapy.

To investigate the effects of the strong cytochrome P450 (CYP) 3A inhibitor itraconazole and the strong CYP3A inducer rifampicin on the pharmacokinetics of single-dose esaxerenone, a nonsteroidal mineralocorticoid receptor blocker, in healthy Japanese subjects.

Pupillography is a noninvasive and cost-effective method to determine autonomic nerve activity. Genetic variants in cytochrome P450 (CYP), dopamine receptor (DRD2, DRD3), serotonin receptor (HTR2A, HTR2C) and ATP-binding cassette subfamily B (ABCB1) genes, among others, were previously associated with the pharmacokinetics and pharmacodynamics of antipsychotic drugs. Our aim was to evaluate the effects of aripiprazole and olanzapine on pupillary light reflex related to pharmacogenetics.

To develop a semi-mechanistic model, based on glutathione depletion and predict a previously identified intra-individual reduction in busulfan clearance to aid in more precise dosing.

Hydrochlorothiazide-induced photosensitivity may increase squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and lip cancer risk. The aim was to quantify these risks.

Explore the efficacy, safety and tolerability of the dual sodium-glucose cotransporter (SGLT) 1 and 2 inhibitor, licogliflozin in patients with type-2 diabetes mellitus (T2DM) and heart failure.

Advanced therapy medicinal products (ATMPs) represent a new category of medicinal products with a potential for transformative improvements in health outcomes but at exceptionally high prices. Routine adoption of ATMPs requires robust evidence of their cost-effectiveness.

The aim of this systematic review was to identify generic instruments for drug discontinuation in patients with polypharmacy in the primary care setting.

Direct-acting antiviral agents (DAAs) for the treatment of hepatitis C (HCV) can be associated with drug-drug interactions (DDIs) with concomitant medications. The practical clinical implications of such DDIs are poorly understood. We assessed the clinical impact of possible pharmacokinetic (PK) interactions between simeprevir and frequently prescribed concomitant medications.

In 2006, Omnitrope (by Sandoz) was the first approved biosimilar in Europe. To date, 21 biosimilars for seven different biologics are on the market. The present study compared the clinical trials undertaken to obtain market authorization.

The Phase Ib GERSHWIN study (NCT01680991) assessed the pharmacokinetic (PK) profile of obinutuzumab following multiple intravenous (i.v.) doses to Chinese patients with B-cell lymphomas, and compared findings with previous obinutuzumab PK studies in mainly Caucasian (non-Chinese) patients.

To assess the effects of a targeted and tailored pharmacist-led intervention among patients with type 2 diabetes (T2DM) who are nonadherent to antihypertensive drugs.