0000000000398143
AUTHOR
Michael Paulzen
Body mass index as a determinant of clozapine plasma concentrations: A pharmacokinetic-based hypothesis
Background: Knowledge regarding the impact of body composition measures on pharmacokinetics of antipsychotics is limited. Aims: Our aim was to investigate the impact of body weight and body mass index on clozapine pharmacokinetics using a therapeutic drug monitoring database. Methods: A large therapeutic drug monitoring dataset of clozapine plasma concentrations considering three patient subgroups was analysed: a control group (CLZ0, 20–30 kg/m2, n=266), a group with high body mass index (CLZhigh, body mass index ⩾30 kg/m2, n=162) and with low body mass index values (CLZlow, body mass index <20 kg/m2, n=27). Comparisons of plasma and dose-adjusted plasma concentrations (C/D) of clozapine…
Opiate-induced dopamine release is modulated by severity of alcohol dependence: an [(18)F]fallypride positron emission tomography study.
Background Preclinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain. Specifically, alcohol-induced release of β-endorphins stimulates μ-opioid receptors (MORs), which is believed to cause dopamine release in the brain reward system. Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol. In the present study, a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effect…
Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system
Investigations on the acute effects of alcohol in the human mesolimbic dopamine D2 /D3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D2 /D3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D2 /D3 receptor ligand [18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D2 /D3 binding potential. Twenty-four healthy male μ-opioid receptor (OPRM1)118G allele carriers underw…
Dopamine D2 Receptor Occupancy Estimated From Plasma Concentrations of Four Different Antipsychotics and the Subjective Experience of Physical and Mental Well-Being in Schizophrenia
Background Impaired subjective well-being in schizophrenia patients treated with antipsychotics has often been linked inter alia to the antidopaminergic effects of medication. Thus, it is important to capture the association between striatal dopamine D2 receptor occupancy (D2-RO) and global subjective well-being. We examined this association using data from our multicenter, randomized, double-blind Neuroleptic Strategy Study (NeSSy). Methods An innovative double randomization process was used for allocation of patients to the specific treatment groups. Plasma drug concentrations were measured after 6 and 24 weeks of treatment to obtain the estimated D2-RO (eD2-RO) relative to literature val…
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017
AbstractTherapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug…
Plasma levels and cerebrospinal fluid penetration by duloxetine in a patient with a non-fatal overdose during a suicide attempt
Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake with weak activity on dopamine reuptake (Wong et al. 1993). Daily doses of 60 mg are effective in the acute treatment of major depression. Duloxetine is extensively metabolized by cytochrome P450 isoenzymes (CYP) 1A2 and to a lesser extent 2D6 (Lobo et al. 2008) to numerous non-active metabolites. Maximum plasma concentration occurs after 6 h, steady-state within 3 d and the mean terminal half-life is 12 h. Fatal outcomes have been reported for acute overdoses as low as 1000 mg, and symptoms of duloxetine overdose are well described. However, information about plasma levels of duloxetine and correspondin…