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 study was a cross-sectional nationwide survey targeting physicians from private medical centres in Malaysia. The survey was conducted using questionnaire having (i) background and demographic data of the physicians, volume of prescription in a day, stock of generic medicines in their hospital pharmacy etc. (ii) their knowledge about bioequivalence (iii) prescribing behavior (iv) physicians' knowledge of quality, safety and efficacy of generic medicines, and their cost (v) perceptions of physicians towards issues pertaining to generic medicines utilization.
RESULTS: A total of 263 questionnaires out of 735 were received, giving a response rate of 35.8%. Of the respondents, 214 (81.4%) were male and 49 (18.6%) were females. The majority of the participants were in the age range of 41-50 years and comprised 49.0% of the respondents. Only 2.3% of physicians were aware of the regulatory limits of bioequivalence standards in Malaysia. Of the respondents, 23.2% agreed that they 'always' write their prescriptions using originator product name whereas 50.2% do it 'usually'. A number of significant associations were found between their knowledge, perceptions about generic medicines and their demographic characteristics.
CONCLUSIONS: The majority of the physicians from private medical centres in Malaysia had negative perceptions about safety, quality and the efficacy of generic medicines. These negative perceptions could be the cause of the limited use of generic medicines in the private medical centres. Therefore, in order to facilitate their use, it is recommended that the physicians need to be reassured and educated about the drug regulatory authority approval system of generic medicines with regard to their bioequivalence, quality, efficacy and safety. Apart from the policy on generic substitution, it would also be recommended to have a national medicine pricing policy, which controls drug prices, in both the public and private sector. These efforts are worthwhile to reduce the drug expenditure and improve the medicine affordability in Malaysia.
RECENT FINDINGS: The quality of multiple generic DAAs has been shown to be bioequivalent to innovator formulations, with generic versions achieving high cure rates in real-world settings. Although published materials are limited, there is expanding experience with local pilot and national treatment programs which are largely being funded by national governments and other institutions.
SUMMARY: Countries and other public health stakeholders are recognizing the need to scale up HCV diagnosis and treatment programs using generic DAAs. However, local pilot or national treatment programs need to be massively expanded to eliminate HCV in high-burden areas.
METHODS: The intrasubject coefficient of variation was estimated from the residual mean square error obtained from analysis of variance of the parameters AUC0-infinity, Cmax and Cmax/AUC0-infinity after logarithmic transformation. The test power in the analyses of the above parameters was subsequently estimated using nomograms provided by Diletti et al. [1991].
RESULTS AND CONCLUSION: Thirty products covering 16 drugs were studied in which 22 were immediate-release (including one dispersible tablet) and 8 were sustained-release formulations. The intrasubject coefficient of variation for the parameter AUC0-infinity was smaller than Cmax, and hence considerably more studies were able to attain a power of greater than 80% using 12 volunteers for the AUC0-infinity, compared to the Cmax. However, the variability in the Cmax could be reduced by using the parameter Cmax/ AUC0-infinity, and thus, provide a more realistic estimation of sample size, since the latter reflects only the rate of absorption and not both the rate and extent as in the case of Cmax [Endrenyi et al. 1991].