RESUMEN
PURPOSE: To evaluate the pharmacokinetic parameters of a single oral dose of vardenafil in patients with pulmonary hypertension (PH). METHODS: Sixteen patients with PH received vardenafil in single oral doses (20, 10 or 5 mg), and repeated blood sampling for up to 9 h was performed. Vardenafil plasma concentration was determined using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using model-independent analysis. RESULTS: The plasma vardenafil concentration increased rapidly and exhibited a median time to maximum plasma concentration (t(max)) of 1 h and a mean elimination half-life (t(1/2)) of 3.4 h. The geometric mean and standard deviation of (1) the peak plasma concentration (C(max)) was 21.4 ± 1.7 µg/L, (2) the normalized C(max) (C(max, norm)) 79.1 ± 1.6 g/L, (3) the area under the time-concentration curve (AUC) 71.5 ± 1.6 µg · h/L and (4) the normalized AUC (AUC(norm)) 261.6 ± 1.7 g · h/L. Patients co-medicated with bosentan reached t(max) later and had a 90% reduction of C(max), C(max, norm), AUC and AUC(norm). CONCLUSION: The pharmacokinetic profile of vardenafil overall revealed considerable inter-individual variability in patients with PH. Co-medication with bosentan resulted in a pharmacokinetic drug interaction, leading to significantly decreased plasma concentrations of vardenafil. Therapeutic drug monitoring for individual dose optimization may be warranted.
Asunto(s)
Hipertensión Pulmonar/sangre , Imidazoles/farmacocinética , Inhibidores de Fosfodiesterasa 5/farmacocinética , Piperazinas/farmacocinética , Vasodilatadores/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Imidazoles/sangre , Masculino , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa 5/sangre , Piperazinas/sangre , Sulfonas/sangre , Sulfonas/farmacocinética , Triazinas/sangre , Triazinas/farmacocinética , Diclorhidrato de Vardenafil , Vasodilatadores/sangreRESUMEN
The effects of clozapine on positive and negative symptoms were studied in 103 patients with treatment-refractory schizophrenia. The evaluation of symptom profile was made before and after clozapine treatment. Overt psychopathology did not vary significantly before clozapine treatment. Significant decreases in positive and negative symptoms were noted by the third month on clozapine. No further significant progress could be observed after 6 months of treatment. No fatal cases were observed, although two patients developed agranulocytosis during clozapine treatment.