Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study.

This study compared decitabine exposure when administered IV (DEC-IV) at a dose of 20 mg/m for 5-days with orally administered decitabine with cedazuridine (DEC-C), as well as the clinical efficacy and safety of DEC-C in patients with acute myeloid leukaemia (AML) who were ineligible for intensive induction chemotherapy. In all, 89 patients were randomised 1:1 to DEC-IV or oral DEC-C (days 1-5 in a 28-day treatment cycle), followed by 5 days of the other formulation in the next treatment cycle. All patients received oral DEC-C for subsequent treatment cycles until treatment discontinuation.

A commentary on the use of pharmacoenhancers in the pharmaceutical industry and the implication for DMPK drug discovery strategies.

Paxlovid, a drug combining nirmatrelvir and ritonavir, was designed for the treatment of COVID-19 and its rapid development has led to emergency use approval by the FDA to reduce the impact of COVID-19 infection on patients.In order to overcome potentially suboptimal therapeutic exposures, nirmatrelvir is dosed in combination with ritonavir to boost the pharmacokinetics of the active product.Here we consider examples of drugs co-administered with pharmacoenhancers.

A validated liquid chromatography-tandem mass spectroscopy method for the quantification of tolinapant in human plasma.

Tolinapant (ASTX660), a pan-selective inhibitor of apoptosis protein antagonist with dual cIAP/XIAP activity, was identified as a clinical candidate in preclinical efficacy, pharmacokinetic and safety studies. In order to assess tolinapant in first-in-human Phase I/II clinical trials, a validated bioanalytical method was required to determine plasma pharmacokinetics. Tolinapant and d-tolinapant were extracted from human plasma using liquid-liquid extraction.