RESUMO
The QT effects of five "QT-positive" and one negative drug were tested to evaluate whether exposure-response analysis can detect QT effects in a small study with healthy subjects. Each drug was given to nine subjects (six for placebo) in two dose levels; positive drugs were chosen to cause 10 to 12 ms and 15 to 20 ms QTcF prolongation. The slope of the concentration/ΔQTc effect was significantly positive for ondansetron, quinine, dolasetron, moxifloxacin, and dofetilide. For the lower dose, an effect above 10 ms could not be excluded, i.e., the upper bound of the confidence interval for the predicted mean ΔΔQTcF effect was above 10 ms. For the negative drug, levocetirizine, a ΔΔQTcF effect above 10 ms was excluded at 6-fold the therapeutic dose. The study provides evidence that robust QT assessment in early-phase clinical studies can replace the thorough QT study.
Assuntos
Fármacos Cardiovasculares/farmacocinética , Fármacos Cardiovasculares/uso terapêutico , Eletrocardiografia/efeitos dos fármacos , Síndrome do QT Longo/tratamento farmacológico , Adulto , Fármacos Cardiovasculares/administração & dosagem , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Modelos Lineares , Síndrome do QT Longo/fisiopatologia , Masculino , Estudos ProspectivosRESUMO
The French national register on in vitro fertilization (IVF) FIVNAT, which has collected most of the oocyte pick-ups realised in France since 1986 has allowed us to build a cohort of 35,714 couples, of which the first recovery took place between 1990 and 1994 and followed up to a pregnancy or to the 31st of december, 1996. The per recovery clinical pregnancy rate decreased from 20.2% on the first attempt to 17.4% on the second, and to less than 13% after the sixth. This evolution existed whatever the women's age class or the infertility diagnosis. The women's age remained the most important factor, since the cumulative pregnancy rate decreased from 60% for women aged less than 35 years to 17% for those aged more than 41 years. Among the indications, male infertility using spouse's semen had the poorest prognosis, especially for women aged more than 41 years (9.6%) whereas male infertility using donor's semen among women aged less than 35 years was associated to the best results (68%). It must be noticed than a high percentage of unpregnant women did not come again for a further recovery (40% to 50%). Then, the crude cumulative birth rate (24.4%) was far below the theoretical cumulative one(54.2%).