ABSTRACT
ABSTRACT: The authors present a case of a 57-year-old patient with chronic myeloid leukemia who was treated with ponatinib and subsequently treated with dasatinib. The patient showed a major molecular response; however, the BCR-ABL1 signal increased with low ponatinib and dasatinib trough concentrations. Cobicistat was used as a pharmacokinetic booster to increase ponatinib and dasatinib exposure, as opposed to increasing the dose. However, ponatinib exposure was not sufficiently increased by cobicistat. The peak dasatinib concentration was successfully increased with cobicistat treatment. Dasatinib and cobicistat cotreatment induced a response in BCR-ABL1 PCR signal, was well tolerated, and led to a substantial reduction in drug costs.
Subject(s)
Antineoplastic Agents , Pyridazines , Humans , Middle Aged , Dasatinib/adverse effects , Cobicistat , Fusion Proteins, bcr-abl/genetics , Imidazoles/adverse effects , Pyridazines/adverse effects , Protein Kinase Inhibitors/adverse effects , Antineoplastic Agents/adverse effectsABSTRACT
The monoclonal antibody infliximab is one of the cornerstones in the treatment of Crohn's disease. Local delivery of infliximab would be an alternative to overcome the inherent disadvantages of intravenous therapy. For this purpose 5mg infliximab tablets were developed. To stabilize the antibody during production and storage it was incorporated in a sugar glass containing the oligosaccharide inulin. To obtain colon-specific release a ColoPulse coating was applied. The tablets were stored for 16 months under different conditions based on ICH climatic zone I.
Subject(s)
Drug Delivery Systems , Excipients/chemistry , Gastrointestinal Agents/administration & dosage , Infliximab/administration & dosage , Chemistry, Pharmaceutical/methods , Colon/metabolism , Crohn Disease/drug therapy , Delayed-Action Preparations , Drug Stability , Drug Storage , Feasibility Studies , Gastrointestinal Agents/chemistry , Infliximab/chemistry , Inulin/chemistry , Tablets , Time FactorsABSTRACT
Respiratory tract infections are among the most common infections in men. We reviewed literature to document their pharmacological treatments, and the extent to which therapeutic drug monitoring (TDM) is needed during treatment. We subsequently examined potential use of dried blood spots as sample procedure for TDM. TDM was found to be an important component of clinical care for many (but not all) pulmonary infections. For gentamicin, linezolid, voriconazole and posaconazole dried blood spot methods and their use in TDM were already evident in literature. For glycopeptides, ß-lactam antibiotics and fluoroquinolones it was determined that development of a dried blood spot (DBS) method could be useful. This review identifies specific antibiotics for which development of DBS methods could support the optimization of treatment of pulmonary infections.
