RESUMEN
BACKGROUND: Aliskiren is the first oral direct renin inhibitor to be approved for the treatment of hypertension. The pharmacokinetic and pharmacodynamic profile of aliskiren has been extensively characterized in Caucasian individuals; however, drug disposition, treatment response and tolerability can vary among ethnic groups, and these variations are difficult to predict. OBJECTIVE: To evaluate the single- and multiple-dose pharmacokinetics of aliskiren in healthy Chinese subjects. METHODS: This was a randomized, single-blind, parallel-group, placebo-controlled study. On day -1, subjects were randomized to one of four cohorts (aliskiren 75, 150, 300 or 600 mg). On day 1, eight individuals in each cohort received a single dose of active treatment and two received placebo. Subjects randomized to aliskiren 300 mg received additional once-daily doses on days 5-11 to establish steady-state pharmacokinetics. Subjects receiving aliskiren 75, 150 or 600 mg (cohorts 1, 2 and 4) completed the study at the end of the 96-hour pharmacokinetic assessment period. Subjects receiving aliskiren 300 mg (cohort 3) had additional pharmacokinetic assessments on days 5-15. The study was carried out at the Peking Union Medical College Hospital, Beijing, China, and included 40 healthy Chinese subjects. The main outcome measures were the pharmacokinetic parameters for aliskiren, including area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)) and maximum plasma concentration (C(max)). RESULTS: Aliskiren AUC(infinity) and C(max) increased greater than proportionally across the 8-fold dose range (75-600 mg; mean AUC(infinity) 291-4726 ng x h/mL, mean C(max) 62-699 ng/mL), but a dose-proportional 2-fold increase was observed within the clinically approved dose range (150-300 mg; mean AUC(infinity) 876-1507 ng x h/mL, mean C(max) 137-271 ng/mL). CONCLUSION: At steady state, the mean AUC during the dosage interval (AUC(tau)) for aliskiren 300 mg (1532 +/- 592 ng x h/mL) was similar to the AUC(infinity) observed following a single dose. Aliskiren exhibits similar single-dose and steady-state pharmacokinetics in Chinese subjects compared with those observed in Caucasian individuals in previous studies.
Asunto(s)
Amidas/farmacocinética , Antihipertensivos/farmacocinética , Fumaratos/farmacocinética , Renina/antagonistas & inhibidores , Administración Oral , Adulto , Amidas/administración & dosificación , Amidas/efectos adversos , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Área Bajo la Curva , Pueblo Asiatico , China , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Femenino , Fumaratos/administración & dosificación , Fumaratos/efectos adversos , Humanos , Masculino , Método Simple Ciego , Adulto JovenRESUMEN
The present randomized, double blind, parallel group, controlled, multi-centric trial was designed to evaluate the efficacy and tolerability of escitalopram in comparison with citalopram and sertraline in the treatment of major depressive disorder. Outpatients (N=214) with an ongoing/newly diagnosed ICD-10 major depressive episode and a Hamilton Rating Scale for Depression (HAM-D) score of > 18 were randomly assigned to citalopram, 20-40 mg/day (74 patients), escitalopram, 10-20 mg/day (69 patients) and sertraline, 50-150 mg/day (71 patients), for a 4-week double-blind treatment period, with dosage adjustment (after 2 weeks of treatment) according to the response to treatment. Clinical response was evaluated by the 17 items HAM-D and the Clinical Global Impression (CGI) scales, which were recorded at baseline and at weekly intervals. Tolerability was evaluated by observed/spontaneously reported adverse changes in laboratory parameters (baseline and after 4 weeks). Response rate was defined as a decrease in HAM-D score by 50% from baseline and remission rate was defined as a HAM-D score of < 8. Response rate at the end of two week were 58% for escitalopram (10mg/day), 49% for citalopram (20mg/day) and 52% for sertraline (50-100mg/day). Response rate at the end of four week were 90% for escitalopram (10-20mg/day), 86% for citalopram (20-40mg/day) and 97% for sertraline (100-150mg/day). The Remission rates at the end of four weeks were 74% for escitalopram, 65% for citalopram and 77% for sertraline. Adverse experiences were reported by 45% of patients in escitalopram group, 58% patients in citalopram and 56% patients in the sertraline group. Additionally, there were lesser dropouts and lesser requirement for dose escalation in escitalopram than in citalopram and sertraline group. In conclusion Escitalopram, the Senantiomer of the citalopram is a safe and effective antidepressant in the Indian population. It has potentially superior efficacy than citalopram and a comparable efficacy to sertraline with fewer side effects than both citalopram and sertraline.