Multiple cytokines for the detection of infection in children with tuberculosis.

Setting: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results.

Objective: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB.

Impact of the CYP2D6 ultra-rapid metabolizer genotype on doxepin pharmacokinetics and serotonin in platelets.

Introduction: CYP2D6 gene duplication causing ultrafast metabolism is one reason for failure in responding to CYP2D6-metabolized antidepressants. We studied the effect of the CYP2D6 duplication genotype on doxepin pharmacokinetics and platelet serotonin uptake and concentrations.

Methods: Pharmacokinetics of trans (E)- and cis (Z)-doxepin and N-desmethyldoxepin were analyzed after a single dose of 75 mg doxepin in 11 ultrafast metabolizers (UM), 11 extensive metabolizers (EM) and 3 poor metabolizers (PM), identified by genotyping for CYP2D6 alleles *2, *3, *4, *5, *6, *9, *10, *35, *41 and specific analyses to characterize gene duplication.

Impact of the CYP2D6 ultrarapid metabolizer genotype on mirtazapine pharmacokinetics and adverse events in healthy volunteers.

Introduction: In vitro studies showed that biotransformation of the antidepressant drug mirtazapine is mediated by cytochrome P-450 enzymes CYP1A2, CYP2D6, and CYP3A4 with CYP2D6 contributing about 35% to total mirtazapine biotransformation. We hypothesized that ultrarapid metabolizers (defined as carriers of the CYP2D6 gene duplication plus another functional allele) have a risk for therapeutic failure due to too low tissue concentrations.

Methods: Ten healthy male volunteers carrying 1 CYP2D6 duplication allele and 1 wild-type allele, 12 carriers of 2 CYP2D6 wild-type alleles and 3 carriers of 2 functionally inactive alleles received a single dose of 45 mg racemic mirtazapine and plasma concentrations were measured from 0 to 58 hours.