Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient under Taxol and granulocyte colony stimulating factor (G-CSF, Neupogen) treatment for metastatic breast carcinoma of the liver experienced repeated suicidal depression on days 10 and 11 of therapy. MRI and MRS were performed during the fifth and sixth cycles of chemotherapy on days 1 and 10. The MRI was normal in all four examinations. The MRS showed normal levels of metabolites on days 1 of therapy, with remarkable reproducible declines in neurobiochemicals myo-inositol (23-27%), choline (20-24%), creatine (10-14%) and glutamate/glutamine (22-39%) on day 10 of therapy. The neurobiochemical declines coincided with the patient's experience of suicidal depression. Patients reporting depression during standard cancer therapy may be experiencing previously undocumented chemotherapeutic neurobiochemical imbalances or neurotoxicity.
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PMID:Neurobiochemical changes from Taxol/Neupogen chemotherapy for metastatic breast carcinoma corresponds with suicidal depression. 901 96

The pharmacokinetic-pharmacodynamic (PK-PD) relationship of the granulopoietic effects of Filgrastim in healthy volunteers was characterized via a population approach. Healthy male volunteers were enrolled into a four-way crossover clinical trial. Subjects received four single doses of Filgrastim (375 and 750 micrograms i.v. and s.c.) with an intervening washout period of 7 days. Serum concentrations of Filgrastim were determined using an enzyme-linked immunosorbent assay. Absolute neutrophil count (ANC) was determined. Data analysis was performed using mixed-effects modeling as implemented in the NONMEM software package. The final PKPD model incorporates a two-compartment PK model with bisegmental absorption from the s.c. site, first-order and saturable elimination pathways, and an indirect PD model. A sigmoidal Emax model for the stimulation of ANC input rate (kin) was superior to the conventional Emax model (mean +/- SE: Emax = 12.7 +/- 1.7; EC50 = 4.72 +/- 0.72 ng/ml; Hill = 1.34 +/- 0.19). In addition, a time-variant scaling factor for ANC observations was introduced to account for the early transient depression of ANC after Filgrastim administration. The absolute bioavailability of subcutaneously administered Filgrastim was estimated to be 0.619 +/- 0.058 and 0.717 +/- 0.028 for 375 micrograms and 750 micrograms s.c. doses, respectively. The time profiles of concentration and ANC, as well as the concentration approximately ANC relationship of Filgrastim in healthy volunteers were well described by the developed population PK-PD model.
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PMID:Population pharmacokinetic-pharmacodynamic modeling of filgrastim (r-metHuG-CSF) in healthy volunteers. 1167 30