Dicloxacillin is an inducer of intestinal P-glycoprotein but neither dicloxacillin nor flucloxacillin increases the risk of stroke/systemic embolism in direct oral anticoagulant users.

Aim: We aimed to assess if dicloxacillin/flucloxacillin reduces the therapeutic efficacy of direct oral anticoagulants (DOACs) and the underlying molecular mechanism.

Methods: In a randomized, crossover study, we assessed whether dicloxacillin reduces oral absorption of drugs through P-glycoprotein (P-gp) during 10 and 28 days of treatment. To study the impact of dicloxacillin/flucloxacillin on intestinal and hepatic expression of P-gp in vitro, we usd LS174T cells and 3D spheroids of primary human hepatocytes.

Flucloxacillin Is a Weak Inducer of CYP3A4 in Healthy Adults and 3D Spheroid of Primary Human Hepatocytes.

Flucloxacillin is a widely used antibiotic. It is an agonist to the nuclear receptor PXR that regulates the expression of cytochrome P450 (CYP) enzymes. Treatment with flucloxacillin reduces warfarin efficacy and plasma concentrations of tacrolimus, voriconazole, and repaglinide.

Neurofilament light chain as a biomarker of axonal damage in sensory neurons and paclitaxel-induced peripheral neuropathy in patients with ovarian cancer.

Paclitaxel-induced peripheral neuropathy (PIPN) is a barrier to effective cancer treatment and impacts quality of life among patients with cancer. We used a translational approach to assess the utility of neurofilament light chain (NFL) as a biomarker of PIPN in a human cell model and in patients with ovarian cancer. We measured NFL in medium from human induced pluripotent stem cell-derived sensory neurons (iPSC-SNs) exposed to paclitaxel.

Drug metabolism and drug transport of the 100 most prescribed oral drugs.

Safe and effective use of drugs requires an understanding of metabolism and transport. We identified the 100 most prescribed drugs in six countries and conducted a literature search on in vitro data to assess contribution of Phase I and II enzymes and drug transporters to metabolism and transport. Eighty-nine of the 100 drugs undergo drug metabolism or are known substrates for drug transporters.

Tutorial: Statistical analysis and reporting of clinical pharmacokinetic studies.

Pharmacokinetics is the cornerstone of understanding drug absorption, distribution, metabolism, and elimination. It is also the key to describing variability in drug response caused by drug-drug interactions (DDIs), pharmacogenetics, impaired kidney and liver function, etc. This tutorial aims to provide a guideline and step-by-step tutorial on essential considerations when designing clinical pharmacokinetic studies and reporting results.

Antimycotic Treatment of Oral Candidiasis in Warfarin Users.

Purpose: Azole antimycotics and nystatin oral solution are used to treat oral candidiasis. Azoles inhibit cytochrome (CYP) P450-dependent metabolism of warfarin, which could increase the anticoagulant effect of warfarin. Nystatin is not expected to interfere with warfarin metabolism, but current data are conflicting.