PMID: 7547256Oct 1, 1995Paper

Bryostatin 1, a novel antineoplastic agent and protein kinase C activator, induces human myalgia and muscle metabolic defects: a 31P magnetic resonance spectroscopic study

British Journal of Cancer
P F HickmanG K Radda

Abstract

Bryostatin 1, a novel antineoplastic agent and protein kinase C (PKC) activator, has been found to induce myalgia (muscle pain) 48 h after administration in clinical trials. This is the dose-limiting toxicity and has restricted the duration of therapy in phase I trials. To investigate the mechanisms and try to increase toleration of the drug, we studied calf muscle metabolism of 14 patients at rest and during exercise and subsequent recovery using 31P magnetic resonance spectroscopy (MRS) before and 4 h, 48-72 h and 1-2 weeks following bryostatin therapy. In resting muscle there was a significant (P < 0.001) increase in the phosphodiester/adenosine 5'-triphosphate (PDE/ATP) ratio 48 h post bryostatin and in patients with myalgia compared with pre-bryostatin control studies. Following exercise, patients with myalgia showed significantly slower phosphocreatine (PCr) and ADP recovery half-time (P < or = 0.05) suggesting impaired mitochondrial (oxidative) energy production, possibly due to a direct effect on the mitochondria or secondary to reduced blood flow. The apparent proton efflux rate following exercise was significantly reduced 4 h after bryostatin (P < or = 0.05), suggesting reduced blood flow. The rate of post-exercise re...Continue Reading

Citations

Jan 23, 2018·The Journal of Clinical Investigation·Szu-Han HuangR Brad Jones
Jul 13, 2006·CNS Drug Reviews·Miao-Kun Sun, Daniel L Alkon
Jan 23, 2004·Cancer Investigation·Jeremy Kortmansky, Gary K Schwartz
Jan 5, 2001·Expert Opinion on Investigational Drugs·P A Philip, J A Zonder
Aug 21, 2002·Anti-cancer Drugs·A Clamp, G C Jayson
Feb 14, 2008·Cancer Chemotherapy and Pharmacology·Geoffrey Y KuGary K Schwartz
Dec 20, 2008·Nature Reviews. Drug Discovery·Tadeusz F MolinskiJonel P Saludes

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