Non-clinical combination toxicology studies: strategy, examples and future perspective.

Over the last decade, combination of drugs in all stages of pharmaceutical development has accelerated availability of promising new therapies for difficult to treat diseases. Safety assessment of combined drugs to be tested in humans can occur at a critical path prior to proceeding in clinical testing. A recent survey by The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ DruSafe) summarized member companies' approaches to combination safety strategies.

Plasma concentrations of three methylated arginines, endogenous nitric oxide synthase inhibitors, in schizophrenic patients undergoing antipsychotic drug treatment.

Plasma concentration of three methylated arginines, endogenous nitric oxide synthase inhibitors, is not studied in schizophrenic patients. The purpose of this study was to determine plasma concentrations of N(G)-monomethyl-L-arginine (l-NMMA), N(G),N(G)-dimethyl-L-arginine (ADMA), N(G),N(G')-dimethyl-L-arginine (SDMA), and l-arginine in 56 male and 45 female schizophrenic patients undergoing antipsychotic drug treatment versus those of 39 male and 24 female healthy controls. Plasma concentrations of methylated arginines and l-arginine were measured using newly developed high performance liquid chromatography with fluorescence detection which we previously reported.