scholarly journals Clozapine Metabolism is Associated With Absolute Neutrophil Count in Individuals With Treatment-Resistant Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Isabella R. Willcocks ◽  
Sophie E. Legge ◽  
Mariana Nalmpanti ◽  
Lucy Mazzeo ◽  
Adrian King ◽  
...  
Keyword(s):  
Immune Cell ◽  
Plasma Concentrations ◽  
Metabolic Ratio ◽  
Genetic Determinants ◽  
Treatment Resistant ◽  
Cell Counts ◽  
Therapeutic Benefits ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Monitoring Service

Up to one-third of those with schizophrenia fail to respond to standard antipsychotics and are considered to have treatment-resistant schizophrenia, a condition for which clozapine is the only evidence-based medication. While up to 60% of treated individuals obtain therapeutic benefits from clozapine, it is currently underprescribed worldwide, partly because of concerns related to its broad adverse effect profile. In particular, the potential effects of clozapine on the immune system have gained relevance after a recent study showed that drug plasma concentrations were inversely correlated with neutrophil counts in individuals routinely undergoing treatment. Seeking to investigate this relationship in more detail, we extracted metabolic, immune, and genetic data from a UK cohort of long-term clozapine users linked to a clozapine monitoring service, CLOZUK2 (N = 208). Whilst a correlation analysis was compatible with the original results, a multiple linear regression accounting for dose and other confounding factors additionally allowed us to estimate the decrease in absolute neutrophil counts to approximately 141 cells/mm3 for every 0.1 mg/L increase in clozapine concentration. However, this association was attenuated after controlling for the metabolic ratio between clozapine and its main metabolite, norclozapine, which was itself negatively associated with neutrophil concentrations. Further analyses revealed that these relationships are likely moderated by genetic factors, as three pharmacogenomic SNPs previously associated to norclozapine plasma concentrations and the metabolic ratio (rs61750900, rs2011425 and rs1126545) were shown to be independently associated with a variation in neutrophil counts of about 400 cells/mm3 per effect allele. Such results are compatible with an effect of norclozapine, but not necessarily clozapine, on immune cell counts, and highlight the need for further investigations into the potential role of genetic determinants of clozapine pharmacokinetics in the occurrence of adverse effects during treatment.

Antiarrhythmic Drug Plasma Concentrations in Ambulatory Patients

1996 ◽  
Vol 30 (3) ◽  
pp. 298-300 ◽  
Author(s):  
Roberto Latini ◽  
Gianna Magnolfi ◽  
Rossella Zordan ◽  
Mariano Ferrari ◽  
Roberto Padrini ◽  
...  
Keyword(s):  
Antiarrhythmic Drug ◽  
Plasma Concentrations ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Ambulatory Patients

Concentration-response relationships for three nonsteroidal anti-inflammatory drugs in the rat intestine

1995 ◽  
Vol 14 (7) ◽  
pp. 573-579 ◽  
Author(s):  
J. Ford ◽  
JB Houston
Keyword(s):  
Rank Order ◽  
Plasma Concentrations ◽  
Intestinal Damage ◽  
Rat Intestine ◽  
Response Data ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Constant Rate ◽  
Inflammatory Drugs ◽  
Intestinal Permeation

1. The effect of diclofenac, piroxicam and (S+)-ibuprofen upon the rat intestine has been measured at constant drug plasma concentrations in the rat, using (51Cr)-EDTA intestinal permeation as a measure of damage. Initially disposition studies after sc administration of the three NSAIDs were carried out. From these studies it was found that constant-rate iv infusions were necessary to maintain plasma concentrations of diclofenac and (S+)-ibuprofen. Administration of piroxicam by sc bolus gave relatively constant plasma concentrations, thus iv infusions were not necessary to obtain concentration-response data for this drug. Relative potency was found by comparing the con centration-response profiles of the three NSAIDs and the rank order of potency obtained was: diclofenac > piroxi cam > (S+)-ibuprofen. 2. The effect of mode of administration upon intestinal damage was also investigated using diclofenac. Intestinal permeability was measured in rats given diclofenac either by sc bolus or iv infusion and dose-response data com pared. It was found that for the same dose, administration by sc bolus gave a higher degree of damage than by iv infusion.

Relationship Between Antiretroviral Drug Plasma Concentrations and Viral Load in Children

2003 ◽  
Vol 32 (1) ◽  
pp. 112-115 ◽  
Author(s):  
J. M. Treluyer ◽  
M. Burgard ◽  
N. Cazali ◽  
P. Quartier ◽  
F. Veber ◽  
...  
Keyword(s):  
Viral Load ◽  
Plasma Concentrations ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Antiretroviral Drug

scholarly journals Neural correlates of the DMT experience assessed with multivariate EEG

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Christopher Timmermann ◽  
Leor Roseman ◽  
Michael Schartner ◽  
Raphael Milliere ◽  
Luke T. J. Williams ◽  
...  
Keyword(s):  
Subjective Experience ◽  
Brain Activity ◽  
Plasma Concentrations ◽  
Oscillatory Activity ◽  
Visual Component ◽  
Eyes Closed ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Oscillatory Power ◽  
Signal Diversity

AbstractStudying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced and neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.

Effect of Long-Term Anti-Hypertensive β-Receptor-Blocking Treatment on Haemodynamic and Metabolic Responses to Prolonged Exercise in Man

1976 ◽  
Vol 51 (s3) ◽  
pp. 489s-491s
Author(s):  
M. Frisk-Holmberg ◽  
A. Juhlin-Dannfeldt ◽  
L. Jorfeldt ◽  
H. Åström
Keyword(s):  
Blood Flow ◽  
Prolonged Exercise ◽  
Plasma Concentrations ◽  
Receptor Blocking ◽  
Leg Blood Flow ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Long Term Treatment ◽  
Β Receptor

1. Central and regional haemodynamics and leg metabolism at rest, during and after a prolonged exercise were studied in seven untreated hypertensive males before and after a long-term treatment (6 weeks) with an unselective β-receptor-blocking drug (alprenolol). 2. Alprenolol treatment (200–400 mg, twice daily) decreased arterial blood pressure at rest and during exercise; it reduced heart rate in relation to drug plasma concentrations during and after exercise; it left cardiac output unchanged; it reduced leg blood flow at rest, but had no effect on leg blood flow during exercise. 3. Alprenolol treatment also decreased lipolysis and lactate release in relation to drug plasma concentrations during exercise.

Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art

2017 ◽  
Vol 43 (04) ◽  
pp. 423-432 ◽  
Author(s):  
Paolo Bianchi ◽  
Marco Ranucci ◽  
Ekaterina Baryshnikova ◽  
Giacomo Iapichino
Keyword(s):  
Point Of Care ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Plasma Concentrations ◽  
Urgent Surgery ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Coagulation Tests ◽  
Before And After

AbstractDirect oral anticoagulants (DOACs) exert similar anticoagulant effects to vitamin K antagonists and are increasingly used worldwide. Nevertheless, an evidence-based approach to patients receiving DOACs when any unplanned urgent surgery or bleeding (either spontaneous or traumatic) occurs is still missing. In this review, we investigate the role of point-of-care coagulation tests when other, more specific tests are not available. Indeed, thromboelastography and activated clotting time can detect dabigatran-induced coagulopathy, while their accuracy is limited for apixaban and rivaroxaban, mostly in cases of low drug plasma concentrations. These tests can also be used to guide the reversal of DOAC-induced coagulopathy providing a quick, before-and-after picture in case of therapeutic use of hemostatic compounds.

Sign in / Sign up

Export Citation Format

Share Document