The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: evaluation using the MDR1A/1B knockout mouse model.

Thirty-two structurally diverse drugs used for the treatment of various conditions of the central nervous system (CNS), along with two active metabolites, and eight non-CNS drugs were measured in brain, plasma, and cerebrospinal fluid in the P-glycoprotein (P-gp) knockout mouse model after subcutaneous administration, and the data were compared with corresponding data obtained in wild-type mice. Total brain-to-plasma (B/P) ratios for the CNS agents ranged from 0.060 to 24.

Frequency of positive studies among fixed and flexible dose antidepressant clinical trials: an analysis of the food and drug administration summary basis of approval reports.

The assumption that the design of an antidepressant clinical trial affects the outcome of that trial is based on sparse data. We sought to examine if the dosing schedule, either a fixed dose or a flexible dose type, in an antidepressant clinical trial affects the frequency with which antidepressants show statistical superiority over placebo. Randomized, placebo-controlled clinical trials of nine antidepressants approved by the Food and Drug Administration between 1985 and 2000 were reviewed.