RESUMEN
In a randomized crossover study, twelve patients presenting a generalized anxiety disorder received either a 1 mg oral tablet or a 1 mg sublingual tablet of lorazepam three times daily for 7 days. After a 7-day washout period, each patient received a 7-day treatment with the other tablet form. Treatments were administered in a double-blind manner using placebos of both the oral and sublingual tablets. Psychiatric evaluations were carried out before and following each of the three periods. Blood samples were drawn at intervals for 48 h following the last dose of each treatment. The plasma concentrations of lorazepam were measured by gas chromatography using an electron-capture detector. Both the oral and sublingual lorazepam produced a significant anxiolytic effect; there was no statistically significant difference between the therapeutic effectiveness of the two forms of lorazepam. The main pharmacokinetic parameters for the oral and sublingual tablets were, respectively: elimination half-life 15.6h and 11.7h; maximal concentration 40.8 ng ml-1 and 42.2 ng ml-1; time to reach maximal concentration 1.2h and 1.4h; corrected area under the curve 310.6 ng hml-1 and 313.6 ng hml-1. There was no statistically significant difference between the oral and sublingual tablets for any of the pharmacokinetic parameters measured.
Asunto(s)
Trastornos de Ansiedad/tratamiento farmacológico , Lorazepam/uso terapéutico , Administración Oral , Administración Sublingual , Adulto , Trastornos de Ansiedad/sangre , Ensayos Clínicos como Asunto , Femenino , Humanos , Lorazepam/administración & dosificación , Lorazepam/farmacocinética , Masculino , Distribución AleatoriaRESUMEN
The use of the calcium antagonist diltiazem (I) is increasing, particularly in treating unstable angina. This study describes a simple and specific high-performance liquid chromatographic method for the determination of I and six of its metabolites in urine. Diltiazem and its conjugated and unconjugated metabolites were assayed in the urine of patients treated with a dose of 120 mg po of diltiazem tid. Sensitivity of the method was 100 ng/mL for I and the metabolites desacetyldiltiazem (II), N-desmethyldesacetyldiltiazem (IV), O-desmethyldesacetyldiltiazem (V), O-desmethyl-N-desmethyldesacetyldiltiazem (VII), N-oxide desacetyldiltiazem (III), and O-desmethyl-N-oxide desacetyldiltiazem (VI). In the urine of patients, the extent of conjugation of six metabolites was greater than 80%.