Enalaprilat is the active metabolite of enalapril. It is the first dicarboxylate-containing ACE inhibitor and was developed partly to overcome these limitations of captopril. The thiol functional group of captopril was replaced with a carboxylic acid group, but additional modifications were required to achieve a potency similar to captopril. Enalaprilat, however, had a problem of its own. The consequence of the structural modifications was that its ionisation characteristics do not allow for sufficient GI absorption. Thus, enalaprilat was only suitable for intravenous administration. This was overcome by the monoesterification of enalaprilat with ethanol to produce enalapril. As a prodrug, enalapril is hydrolyzed in vivo to the active form enalaprilat by various esterases. Peak plasma enalaprilat concentrations occur 2 to 4 hours after oral enalapril administration. Elimination thereafter is biphasic, with an initial phase which reflects renal filtration (elimination half-life 2 to 6 hours) and a subsequent prolonged phase (elimination half-life 36 hours), the latter representing equilibration of drug from tissue distribution sites. The prolonged phase does not contribute to drug accumulation on repeated administration but is thought to be of pharmacological significance in mediating drug effects. Renal impairment [particularly creatinine clearance < 20 ml/min (< 1.2 L/h)] results in significant accumulation of enalaprilat and necessitates dosage reduction. Accumulation is probably the cause of reduced elimination in healthy elderly individuals and in patients with concomitant diabetes, hypertension and heart failure. == References ==
Lisocabtagene maraleucel, sold under the brand name Breyanzi, is a cell-based gene therapy used to treat large B-cell lymphoma.Side effects include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system. The most common side effects include decreases in neutrophils (a type of white blood cell that fights infections), in red blood cells or in blood platelets (components that help the blood to clot), as well as cytokine release syndrome (a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain and low blood pressure) and tiredness.Lisocabtagene maraleucel, a chimeric antigen receptor (CAR) T cell (CAR-T) therapy, is the third gene therapy approved by the U.S. Food and Drug Administration (FDA) for certain types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Lisocabtagene maraleucel was approved for medical use in the United States in February 2021.