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Four basic models for characterizing indirect pharmacodynamic responses after drug administration have been developed and compared. The models are based on drug effects (inhibition or stimulation) on the factors controlling either the input or the dissipation of drug response. Pharmacokinetic parameters of methylprednisolone were used to generate plasma(More)
Kidney is a major target for adverse effects associated with corticosteroids. A microarray dataset was generated to examine changes in gene expression in rat kidney in response to methylprednisolone. Four control and 48 drug-treated animals were killed at 16 times after drug administration. Kidney RNA was used to query 52 individual Affymetrix chips,(More)
Elevated systemic levels of glucocorticoids are causally related to peripheral insulin resistance. The pharmacological use of synthetic glucocorticoids (corticosteroids) often results in insulin resistance/type II diabetes. Skeletal muscle is responsible for close to 80% of the insulin-induced systemic disposal of glucose and is a major target for(More)
Pharmacodynamics is the study of the time course of pharmacological effects of drugs. The field of pharmacodynamic modeling has made many advances, due in part to the relatively recent development of basic and extended mechanism-based models. The purpose of this article is to describe the classic as well as contemporary approaches, with an emphasis on(More)
Target-mediated drug disposition (TMDD) usually accounts for nonlinear pharmacokinetics (PK) of drugs whose distribution and/or clearance are affected by their targets owing to high affinity and limited capacity. TMDD is frequently reported for monoclonal antibodies (mAb) for such reason. Minimal physiologically-based pharmacokinetic models (mPBPK), which(More)
The metyrapone test, a useful and reliable procedure for assessing hypothalamic-pituitary-adrenocortical (HPA) axis function, was applied to schizophrenic patients and healthy controls. 4 out of 18 patients had subnormal responses to metyrapone whereas there were no such cases in the 22 control subjects. 1 schizophrenic patient and 3 control subjects had(More)
BACKGROUND Microarray technology is a powerful and widely accepted experimental technique in molecular biology that allows studying genome wide transcriptional responses. However, experimental data usually contain potential sources of uncertainty and thus many experiments are now designed with repeated measurements to better assess such inherent(More)
The metyrapone test was applied to patients suffering from major depressive illness with melancholia, from mania, and from schizophrenia. Hypoactivity of the HPA axis as assessed by the test appears to occur infrequently in affective disorders and schizophrenia. High normal or exaggerated responses to metyrapone, as observed in Cushing's disease, appear to(More)
  • Abbott, David H Abman, Steven H Acker, Helmut Adhihetty, Peter Agostoni, Piergiuseppe Ahima +494 others
  • 2011
Reviewers The Publications Committee of the American Physiological Society gratefully acknowledges the services of the following reviewers who assisted the Editorial Board in the reviews of manuscripts. (invited only) have specific instructions that you should review if you are submitting to them. The American Physiological Society (APS) Journals seek(More)
R2 Investigating the origins of variability in drug response at the single-cell, organ and patient level based on proteomic, genomic and environmental differences .. R5: Reconnecting tissue physiology with chemistry to facilitate pharmacological experimentation and phenotypic screening on complex systems (cells and model organisms .. R7: Developing(More)