ABSTRACT
PURPOSE: To report a case involving a patient with presumed panretinal ritonavir-induced retinopathy. METHODS: A 52-year-old, HIV-positive patient, with no criteria for AIDS associated with the use of ritonavir for more than 10 years, underwent clinical examination, fundus photography, spectral domain optical coherence tomography, and fundus autofluorescence imaging. RESULTS: Fundus examination revealed areas of atrophy and hypertrophy in the retinal pigment epithelium throughout the retina. Laboratory tests for other diseases were all negative. CONCLUSION: HIV-positive patients undergoing ritonavir therapy should be carefully followed in the presence of low-acuity vision complaints and retinal changes.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , HIV , Retinal Diseases/chemically induced , Retinal Pigment Epithelium/pathology , Ritonavir/adverse effects , Visual Acuity , Fluorescein Angiography/methods , Follow-Up Studies , Fundus Oculi , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/therapeutic use , Humans , Male , Middle Aged , Retinal Diseases/diagnosis , Ritonavir/therapeutic use , Time Factors , Tomography, Optical Coherence/methodsABSTRACT
Myclobutanil is a chiral triazole fungicide that is employed worldwide. Although enantiomers have the same physical-chemical properties, they may differ in terms of activity, metabolism, and toxicity. This investigation consisted of in vitro enantioselective metabolism studies that employed a human model to assess the risks of myclobutanil in humans. A LC-MS/MS enantioselective method was developed and validated. The enzymatic kinetic parameters (VMAX, KMapp, and CLINT) determined for in vitro rac-myclobutanil and S-(+)-myclobutanil metabolism revealed enantioselective differences. Furthermore, human CYP450 enzymes did not metabolize R-(-)-myclobutanil. The predicted in vivo toxicokinetic parameters indicated that S-(+)-myclobutanil may be preferentially eliminated by the liver and suffer the first-pass metabolism effect. However, because CYP450 did not metabolize R-(-)-myclobutanil, this enantiomer could reach the systemic circulation and stay longer in the human body, potentially causing toxic effects. The CYP450 isoforms CYP2C19 and CYP3A4 were involved in rac-myclobutanil and S-(+)-myclobutanil metabolism. Although there were differences in the metabolism of the myclobutanil enantiomers, in vitro inhibition studies did not show significant enantioselective differences. Overall, the present investigation suggested that myclobutanil moderately inhibits CYP2D6 and CYP2C9 in vitro and strongly inhibits CYP3A and CYP2C19 in vitro. These results provide useful scientific information for myclobutanil risk assessment in humans.
Subject(s)
Cytochrome P-450 Enzyme Inhibitors/toxicity , Cytochrome P-450 Enzyme System/metabolism , Fungicides, Industrial/toxicity , Nitriles/toxicity , Triazoles/toxicity , Chromatography, Liquid , Cytochrome P-450 Enzyme Inhibitors/pharmacokinetics , Fungicides, Industrial/pharmacokinetics , Humans , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Nitriles/chemistry , Nitriles/pharmacokinetics , Reproducibility of Results , Stereoisomerism , Tandem Mass Spectrometry , Toxicokinetics , Triazoles/chemistry , Triazoles/pharmacokineticsABSTRACT
PURPOSE: To determine the optimal interval between competitions for success in the different events of the judo world tour. METHODS: A total of 20,916 female and 29,900 male competition participations in the judo world-tour competitions held between January 2009 and December 2015 were analyzed, considering the dependent variable, winning a medal, and the independent variables, levels of competition. RESULTS: There was an increased probability of winning a medal when the interval was in the 10- to 13-wk range for both male and female athletes competing at Grand Prix, Continental-Championship, and World-Championship events, whereas for Grand Slam, only men had an increased probability of winning a medal in this interval range. Furthermore, men had increased probability of podium positions in Continental Championship, World Master, and Olympic Games when the interval was longer than 14 wk. CONCLUSION: Optimal interval period between successive competitions varies according to competition level and sex; shorter intervals (6-9 wk) were better for female athletes competing at the lowest competition level (Continental Open), but for most of the competitions, the 10- to 13-wk interval was detected as optimal for both male and female athletes (Grand Prix, Continental Championship, and World Championship), whereas for the ranking-based qualified male competitions (ie, Masters and Olympic Games), a longer period (>14 wk) is needed.
