RESUMO
Several reports have demonstrated that the efficacy of latanoprost is influenced by the time of dosing. This model-based meta-analysis validates previous findings that evening dosing is superior to morning dosing and predicts the optimal time for dosing, based on the quantitative assessment of baseline and latanoprost-treated 24-h circadian intraocular pressure (IOP) curves. The results confirm the importance of the time of dosing as a factor that influences the extent of reduction in IOP and underline the need to take this factor into consideration in the design of glaucoma trials and therapy.
Assuntos
Anti-Hipertensivos/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Prostaglandinas F Sintéticas/administração & dosagem , Anti-Hipertensivos/farmacologia , Ritmo Circadiano , Esquema de Medicação , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Latanoprosta , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Prostaglandinas F Sintéticas/farmacologiaRESUMO
To assess the QTc prolongation by ritonavir (RTV) 100 mg and explore its potential use as CYP3A inhibitor in thorough QTc (TQT) studies. Randomized, crossover study of single-dose RTV 100 mg, placebo, and moxifloxacin (MFLX) 400 mg in 65 healthy subjects with serial triplicate electrocardiograms obtained for 12 h post-dose. Largest mean placebo-adjusted QTcF increase from baseline (90% confidence interval (CI)) for RTV 100 mg was noninferior to placebo (0.16 ms (-1.38, 1.69)). Study sensitivity was validated by detecting the largest mean placebo-adjusted QTcF increase from baseline (90% CI) for MFLX of 8.31 ms (6.44, 10.18). A single dose of RTV 100 mg does not cause QTc prolongation in healthy subjects. Based on the potent CYP3A4 inhibition, lack of QTc effect and better safety profile, RTV 100 mg could replace ketoconazole as the CYP3A4 inhibitor in TQT studies.