Dose-response relationships are not fully understood for antipsychotics. Especially in the case of multimodal antipsychotics, these relationships cannot be simplified to the level of dopaminergic receptor occupancy alone. In general, for most antipsychotics, there is no linear dose-response relationship. Reasons for this include, among others, pharmacokinetic factors affecting plasma levels. Based on meta-analyses, the doseresponse curve appears to be bell-shaped. However, in the case of some antipsychotics, it appears that even increasing the dose beyond the recommended range could yield further increases in efficacy. It should be stressed that this is an off-label procedure and cannot generally be recommended and there is not enough valid information for general conclusions for these antipsychotics either. Mini-invasive sampling and alternative matrices such as saliva or dry blood spots could open the way to more frequent monitoring of antipsychotics and a better understanding of doseresponse relationships.
- Klíčová slova
- Safety, Therapeutic drug monitoring, dose- response relationship, efficacy, lurasidone, safety,
- MeSH
- antipsychotika * terapeutické užití MeSH
- lidé MeSH
- lurasidon hydrochlorid terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antipsychotika * MeSH
- lurasidon hydrochlorid MeSH
Dose-response relationships are not fully understood for antipsychotics. Especially in the case of multimodal antipsychotics, these relationships cannot be simplified to the level of dopaminergic receptor occupancy alone. In general, for most antipsychotics, there is no linear dose-response relationship. Reasons for this include, among others, pharmacokinetic factors affecting plasma levels. Based on meta-analyses, the doseresponse curve appears to be bell-shaped. However, in the case of some antipsychotics, it appears that even increasing the dose beyond the recommended range could yield further increases in efficacy. It should be stressed that this is an off-label procedure and cannot generally be recommended and there is not enough valid information for general conclusions for these antipsychotics either. Mini-invasive sampling and alternative matrices such as saliva or dry blood spots could open the way to more frequent monitoring of antipsychotics and a better understanding of doseresponse relationships.
- Klíčová slova
- Safety, Therapeutic drug monitoring, dose- response relationship, efficacy, lurasidone, safety,
- MeSH
- antipsychotika * terapeutické užití MeSH
- lurasidon hydrochlorid terapeutické užití MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antipsychotika * MeSH
- lurasidon hydrochlorid MeSH
Imatinib mesylate is a competitive inhibitor of BCR/ ABL tyrosine kinase and inhibits also several receptor tyrosin kinases. Since its launch to the market, imatinib has proven to be very valuable in the treatment of Philadelphia chromosome (BCR/ ABL) - positive (Ph+) chronic myeloid leukemia and Kit (CD117) positive gastrointestinal stromal tumors. The drug is metabolized by cytochrome P450, and there are many clinically important pharmacokinetic drug-drug interactions described in the literature. Frequent polypharmacy in oncological patients increases probability of such interactions, and also adherence may play its role during longterm treatment. Fixed dosing therapeutic regimens fail to respect known interindividual variability in pharmacokinetics of the drug and thus, some patients may not achieve sufficient plasma concentrations. Based on current evidence, there seems to be a relationship between plasma concentration and clinical response to imatinib. Therefore, imatinib appears to be suitable candidate for therapeutic drug monitoring. Here, we present an overview of pharmacokinetics, drug-drug interactions and current knowledge and suggestions on therapeutic drug monitor-ing of imatinib, its potential benefits and limitations.
- MeSH
- benzamidy krev farmakokinetika terapeutické užití MeSH
- chronická myeloidní leukemie farmakoterapie MeSH
- gastrointestinální stromální tumory farmakoterapie MeSH
- imatinib mesylát MeSH
- inhibitory proteinkinas krev farmakokinetika terapeutické užití MeSH
- lidé MeSH
- monitorování léčiv * MeSH
- piperaziny krev farmakokinetika terapeutické užití MeSH
- pyrimidiny krev farmakokinetika terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- benzamidy MeSH
- imatinib mesylát MeSH
- inhibitory proteinkinas MeSH
- piperaziny MeSH
- pyrimidiny MeSH
Safranal and crocin are biologically active compounds isolated from Crocus sativus L., commonly known as saffron. Clinical trials confirm that saffron has antidepressant effect, thus being a potential valuable alternative in the treatment of depression. The aim of the present study was to determine, whether systemic administration of safranal and crocin can influence the metabolic activity of CYP3A, CYP2C11, CYP2B, and CYP2A in rat liver microsomes (RLM). The experiments were carried out on male Wistar albino rats intragastrically administered with safranal (4, 20, and 100 mg/kg/day) or with intraperitoneal injections of crocin (4, 20, and 100 mg/kg/day). Our results demonstrate the ability of safranal and crocin to increase the total protein content and to change the metabolic activity of several CYP enzymes assessed as CYP specific hydroxylations of testosterone in RLM. Crocin significantly decreased the metabolic activity of all selected CYP enzymes, while safranal significantly increased the metabolic activity of CYP2B, CYP2C11 and CYP3A enzymes. Therefore, both substances could increase the risk of interactions with co-administered substances metabolized by cytochrome P450 enzymes.
- MeSH
- aktivace enzymů účinky léků fyziologie MeSH
- Crocus * MeSH
- cyklohexeny izolace a purifikace farmakologie MeSH
- jaterní mikrozomy účinky léků enzymologie MeSH
- karotenoidy izolace a purifikace farmakologie MeSH
- krysa rodu Rattus MeSH
- potkani Wistar MeSH
- rostlinné extrakty izolace a purifikace farmakologie MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- terpeny izolace a purifikace farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- crocin MeSH Prohlížeč
- cyklohexeny MeSH
- karotenoidy MeSH
- rostlinné extrakty MeSH
- safranal MeSH Prohlížeč
- systém (enzymů) cytochromů P-450 MeSH
- terpeny MeSH
