Phenoconversion of CYP2D6 by inhibitors modifies aripiprazole exposure.

The efficacy of aripiprazole therapy and the risk of adverse reactions are influenced by substantial inter-individual variability in aripiprazole metabolizing capacity. In vitro studies assigned the potential role in aripiprazole metabolism to CYP2D6 and CYP3A enzymes; therefore, the association between the steady-state aripiprazole plasma concentrations and patients' CYP2D6 and CYP3A statuses (CYP2D6, CYP3A4, and CYP3A5 genotypes, and CYP3A4 expression) and/or co-medication with CYP function modifying medications has been investigated in 93 psychiatric patients on stable aripiprazole therapy. The patients' CYP2D6 genotype had a major effect on aripiprazole plasma concentrations, whereas contribution of CYP3A genotypes and CYP3A4 expression to aripiprazole clearance were considered to be minor or negligible. The role of CYP3A4 expression in aripiprazole metabolism did not predominate even in the patients with nonfunctional CYP2D6 alleles. Furthermore, dehydroaripiprazole exposure was also CYP2D6 genotype-dependent. Dehydroaripiprazole concentrations were comparable with aripiprazole levels in patients with functional CYP2D6 alleles, and 35% or 22% of aripiprazole concentrations in patients with one or two non-functional CYP2D6 alleles, respectively. The concomitant intake of CYP2D6 inhibitors, risperidone, metoprolol, or propranolol was found to increase aripiprazole concentrations in patients with at least one wild-type CYP2D6*1 allele. Risperidone and 9-hydroxy-risperidone inhibited both dehydrogenation and hydroxylation of aripiprazole, whereas metoprolol and propranolol blocked merely the formation of the active dehydroaripiprazole metabolite, switching towards the inactivation pathways. Patients' CYP2D6 genotype and co-medication with CYP2D6 inhibitors can be considered to be the major determinants of aripiprazole pharmacokinetics. Taking into account CYP2D6 genotype and co-medication with CYP2D6 inhibitors may improve the outcomes of aripiprazole therapy.

Screening of mecI Gene in Staphylococcus Strains Isolated in Transylvania Region of Romania.

In the last few decades, methicillin-resistant Staphylococcus aureus (MRSA) strains have become a serious health care problem. However, in the European Union/European Economic Area countries the prevalence of the invasive MRSA isolates has decreased in recent years; in Romania, the considerably high prevalence of these strains is still unchanged. In this study, 396 staphylococcal strains were screened using molecular biology techniques for the presence of the nucA, mecA, and mecI genes and for the detection of the possible mutations accumulated in the mecI gene. More than half of the collected Staphylococcus strains (59.34%) were determined as S. aureus, and 63 strains were considered as MRSA. Small number of MRSA strains (n = 6; 54.54% of invasive S. aureus) originated from hemoculture. The mecI gene was present in 22 MRSA strains and in 4 methicillin-resistant coagulase-negative staphylococci strains. The majority of the mecI-positive MRSA strains contained the C to T substitution at position 202; furthermore, one previously undescribed mutation (C to G transversion at nucleotide position 285) was detected in one MRSA strain.