The role of drug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP) and OATP1A/1B and of CYP3A4 in the pharmacokinetics of the CDK inhibitor milciclib.

The promising anticancer drug milciclib potently inhibits cyclin-dependent kinase (CDK) 2 and tropomyosin receptor kinase (TRK) A, and is currently in phase II clinical studies. To characterize factors affecting milciclib pharmacokinetics, we investigated whether milciclib is a substrate of the multidrug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP), and OATP1A/1B, and the drug-metabolizing enzyme CYP3A, using genetically-modified mouse models and Madin-Darby Canine Kidney (MDCK-II) cells. In vitro, milciclib was transported by mAbcg2, and this was inhibited by the ABCG2 inhibitor Ko143.

Reprint of: The effects of decomposition and environment on antemortem H-Pb-Sr isotope compositions and degradation of human scalp hair: Actualistic taphonomic observations.

Multi-isotope analysis (e.g., Sr-Pb-O-H-C-N) of human scalp hair is routinely used in forensic investigations of human remains to constrain the geographic origin of unidentified bodies, and to investigate antemortem mobility patterns.

Development and validation of an LC-MS/MS method for the quantitative analysis of milciclib in human and mouse plasma, mouse tissue homogenates and tissue culture medium.

Milciclib is a promising cyclin-dependent kinase inhibitor currently in phase II clinical trials to treat several types of cancer. The first bioanalytical method for the quantitative analysis of milciclib in several biomatrices using liquid chromatography-tandem mass spectrometry is described here. This method was fully validated in human plasma according to FDA and EMA guidelines, and partially validated in mouse plasma, homogenates of mouse brain, kidney, liver, small intestine, spleen, and tissue culture medium.

The effects of decomposition and environment on antemortem H-Pb-Sr isotope compositions and degradation of human scalp hair: Actualistic taphonomic observations.

Multi-isotope analysis (e.g., Sr-Pb-O-H-C-N) of human scalp hair is routinely used in forensic investigations of human remains to constrain the geographic origin of unidentified bodies, and to investigate antemortem mobility patterns.