MATERIALS AND METHODS: A randomized, 2-treatment, 2-period, 2-sequence, single dose, crossover with a washout period of 2 weeks, was conducted in 24 healthy Thai male volunteers. Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h following drug administration. Plasma concentrations of risperidone and 9-hydroxyrisperidone were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of risperidone and 9-hydroxyrisperidone were determined using a non-compartmental model.
RESULTS: The geometric means ratios (%) and 90% confidence interval (CI) of the test and reference products for the log-transformed pharmacokinetic parameters, Cmax, AUC0-t and AUC0-inf of risperidone were 104.49 % (92.79% - 117.66%), 100.96 % (92.15% - 110.61 %) and 97.99 % (90.72% - 105.85%). The 90% CI of geometric means ratios of the test and reference products for the log-transformed pharmacokinetic parameters, Cmax, AUC0-t and AUC0-inf of 9-hydroxyrisperidone were 97.00%, 96.97% and 97.49%.
CONCLUSIONS: The 90% CI for the geometric means ratios (test/reference) of the log-trasformed Cmax, AUC0-t and AUC0-inf of risperidone and its major active metabolite were within the bioequivalence acceptance criteria of 80% - 125% of the US-FDA.
METHODS: This was a cross-sectional study conducted among Malaysian adults in three northern states of Malaysia. A pre-developed questionnaire consisting of both the EQ-5D and SF-12 items was used for data collection. Concurrent, convergent, and known group validity of EQ-5D were assessed against SF-12 and several known relationships with participants' demographic and illness characteristics.
RESULTS: A total of 596 Malaysians participated in the study. The mean EQ-5D score was 0.93 (SD = 0.13), while the mean physical component score (PCS-12) and mental component score (MCS-12) scores were 48.9 (SD = 7.4) and 49.1 (SD = 8.0), respectively. Participants with a current medical problem had lower PCS-12 and MCS-12 scores and reported more problems with all of the EQ-5D dimensions; they also had lower EQ-5D and EQ-VAS scores (P < 0.05). Convergent validity was supported by a moderately positive correlation between EQ-5D and EQ-VAS with MCS-12 and PCS-12 scores; moreover, the stronger effect sizes between PCS-12 and the physical dimensions of EQ-5D as well as between MCS-12 with anxiety/depression scores further supported the convergent validity of EQ-5D. Responses to the EQ-5D dimensions only supported two of the four known group validity hypotheses of higher quality of life among individuals who are better educated and no medical problem. No association was found between income and gender with EQ-5D score.
CONCLUSION: This study has demonstrated acceptable construct validity of the EQ-5D among the Malaysian population.