Current Drug Metabolism - Volume 21, Issue 13, 2020

Background: As a new tumor therapy, targeted therapy is becoming a hot topic due to its high efficiency and low toxicity. Drug effects of targeted tumor drugs are closely related to pharmacokinetics, so it is important to understand their distribution and metabolism in vivo. Methods: A systematic review of the literature on the metabolism and distribution of targeted drugs over the past 20 years was conducted, and the Read More

Background: The kidneys are vital organs acting as the body’s filters that eliminate drugs and other waste products from the body. For effective cancer therapy, a delicate balance is required in the drug treatment and its elimination, which is critical for drug accumulation, toxicity, and kidney malfunction. However, how renal cell carcinoma (RCC) affects the kidneys in safely eliminating the byproducts of drug treatments in pati Read More

Background: Dasatinib, as an oral multi-targeted inhibitor of BCR-ABL and SRC family kinases, has been widely used for the treatment of Philadelphia Chromosome Positive Leukemias in imatinib-acquired resistance and intolerance. The study aimed to develop and validate a simple and robust assay with a small volume of plasma based on liquid chromatography coupled with tandem mass spectrometry to determine Read More

Background: Desloratadine is a drug with a phenotypic polymorphism in metabolism and has been approved for use in many countries to treat allergic diseases. CYP2C8 and UGT2B10 are metabolic enzymes, which may be involved in the metabolism of desloratadine. Objective: This study aimed to demonstrate bioequivalence between the test product (desloratadine tablet) and the reference product AERIUS (5mg), both or Read More

Background: Retrorsine is one of the hepatotoxic pyrrolizidine alkaloids, which could be converted into a highly reactive metabolite, dehydroretrorsine, by CYP3A, and to a lesser extent by CYP2C and CYP2B. Objective: We employed Cyp3a knockout (3AKO) mice to investigate whether the absence of CYP3A could attenuate dehydroretrorsine formation and the role of CYP2C and CYP2B in the formation. Method Read More

Background: The large interindividual variability in the genetic polymorphisms of sirolimus (SIR)- metabolizing enzymes, transporters, and receptors can lead to qualitatively and quantitatively distinct therapeutic responses. Objective: We examined the impact of numerous candidate single-nucleotide polymorphisms (SNPs) involved in the trough concentration of SIR-based immunosuppressant regimen. Methods: This is a ret Read More

Background: Leonurine (Leo), a promising antilipemic agent that has been approved for clinical trials, is extensively metabolized into bioactive Leonurine-10-O-β-glucuronide (L-10-G) vivo. Objective: To explore the effects of breast cancer resistance protein (Bcrp) and multidrug resistance protein 2 (Mrp2) on the disposition of L-10-G. Methods: The pharmacokinetics, tissue distribution and intestinal perfusion of Leo were stu Read More