RESUMO
BACKGROUND: Utilization of Thai traditional medicine (TTM) was considered in menstrual-cycle-related signs and symptoms (MCSs) to evaluate women's health. TTM clinicians diagnosed the MCSs by signs, symptoms, and associated factors of patients including a physical examination to find patterns of imbalance elements and the origin of the disorder to optimize treatment. Thus, the purpose of this study was to develop a new assessment tool, the menstrual-cycle-related signs and symptoms questionnaire (MCSQ) based on TTM principles for evaluation of women's menstrual health. METHODS: The items and components of the MCSQ were adjusted by TTM expert consensus using the Delphi technique. The content validity of the MCSQ was quantified by the content validity index (CVI). MCSQ were examined by construct validity and internal consistency reliability using exploratory factor analysis (EFA) and Cronbach's α coefficient, respectively. RESULTS: : All 19 experts (100%) responded to the questionnaires in the three rounds of the Delphi technique. The MCSQ showed high content validity of individual items (I-CVI = 0.83-1.00) and high overall content validity of the questionnaire (S-CVI/AVE = 0.98). Overall, 429 of 432 participants completed the questionnaire (99.31%). After factor analysis, the final MCSQ was divided into two sections, which consisted of 49 items. The first had 23 items focusing on the MCSs. And, the second had 14 items of personal and medical data including 12 items of associated factors. Cronbach's α coefficient of the final MCSQ was 0.87, and that of each component was between 0.32 and 0.82. CONCLUSIONS: This study reports a new MCS questionnaire tool, which was developed from TTM knowledge to evaluate women's health. This questionnaire showed an acceptable level of validity and reliability. Thus, it is also expected to be useful in clinical practice and ongoing research on evaluation of women's health.
RESUMO
BACKGROUND: Data regarding the pharmacokinetic properties of risperidone in the Thai population are limited. A new generic tablet formulation was recently developed, but bioequivalence research is necessary to obtain marketing authorization for it in Thailand. OBJECTIVE: The aim of this study was to evaluate and compare the pharmacokinetic properties of risperidone and its active metabolite, 9-hydroxyrisperidone (which reportedly contributes to the drug's pharmacodynamic effects), in a newly developed generic tablet formulation (test) and a branded formulation (reference) in healthy, fasting, male Thai volunteers. METHODS: A single-dose, randomized-sequence, double-blind, 2-way crossover design was used in this study. The study took place from October 21 through November 28, 2007. After a ≥10-hour overnight fast, volunteers were orally administered one 2-mg risperidone tablet, either the test formulation (Condrug International Company, Ltd.) or the reference formulation-according to the randomization schedule-followed by a 14-day washout period and administration of the alternate formulation. Blood samples were collected over a period of 96 hours. Risperidone and 9-hydroxyrisperidone plasma concentrations were simultaneously determined using a validated HPLC/ion trap mass spectrometry method. The plasma concentration-time curves of the active moiety, risperidone, and 9-hydroxyrisperidone were generated for each volunteer, from which the C(max), T(max), AUC0â(last), AUC0â(∞), and t(½) were determined using noncompartmental analysis. The effects of formulation, period, sequence, and subject (within sequence) on pharmacokinetic parameters were analyzed using ANOVA. According to regulatory requirements set forth by Thailand, the Association of Southeast Asian Nations, and the US Food and Drug Administration, products meet the criteria for bioequivalence if the 90% CIs of the treatment ratios for C(max) and AUC are within the range of 0.80 to 1.25. Tolerability was assessed by patient interview, monitoring vital signs (ie, resting blood pressure, heart rate, body temperature), physical examination, and laboratory tests (ie, urinalysis, hematology, blood chemistry) before and after the study. RESULTS: A total of 22 Thai male volunteers (mean [SD] age, 28.18 [8.27] years [range, 20.62-44.19 years]; weight, 62.43 [4.76] kg [range, 55.03-76.02 kg]; and body mass index, 21.76 [2.07] kg/m² [range, 18.9924.91 kg/m²]) completed the study. The mean (SD) relative bioavailabilities of test to reference formulations determined from AUC of the active moiety, risperidone, and 9-hydroxyrisperidone were 1.06 (0.18), 1.07 (0.29), and 1.04 (0.17), respectively. The ANOVA suggested no statistically significant effect of formulation, period, or sequence on the studied pharmacokinetic parameters of the active moiety, risperidone, or 9-hydroxyrisperidone. The 90% CIs for the natural logarithm-transformed ratios of C(max), AUC0â(last), and AUC0â(∞) were as follows: for active moiety, 0.94 to 1.03, 0.98 to 1.11, and 0.98 to 1.10, respectively; for risperidone, 0.90 to 1.10, 0.96 to 1.13, and 0.96 to 1.14, respectively; and for 9-hydroxyrisperidone, 0.91 to 1.03, 0.97 to 1.10, and 0.96 to 1.09, respectively. All met the criteria for bioequivalence. The most commonly reported adverse events (AEs) were somnolence (100.0%), orthostatic hypotension (13.6%), headache (4.5%), and syncope (2.3%). AEs were mild and disappeared within 1 day. No volunteers withdrew from the study because of AEs. CONCLUSIONS: The single-dose pharmacokinetic data in this small, all-male, selected sample of fasting, healthy volunteers met Thailand's regulatory criteria for assuming bioequivalence of the tested generic and reference 2-mg risperidone tablets. Both formulations were well tolerated.