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.
METHOD: The effects of organic modifiers in mobile phase, protein precipitation agent to plasma sample ratio, and light on montelukast stability in unprocessed and processed human plasma, were evaluated. Validation was conducted in accordance with European Medicines Agency Guideline on bioanalytical method validation.
RESULTS: No interference peak was observed when acetonitrile was used as an organic modifier. Acetonitrile to plasma ratio of 4:1 produced clean plasma sample. Approximately 3 % of cis isomer was detected in unprocessed plasma samples while 21 % of cis isomer was detected in processed plasma samples after exposing to fluorescent light for 24h. The standard calibration curve was linear over 3.00-1200.00 ng/mL. All method validation parameters were within the acceptance criteria.
CONCLUSION: The validated method was successfully applied to a bioequivalence study of two montelukast formulations involving 24 healthy Malaysian volunteers. The light stability of a light sensitive drug in unprocessed and processed human plasma samples should be studied prior to pharmacokinetic/bioequivalence studies. Measures could then be taken to protect the analyte in human plasma from light degradation.
SETTING: A sample of 1419 Malaysian community pharmacies with resident pharmacists.
METHOD: A cross-sectional nationwide survey using a self-completed mailing questionnaire.
MAIN OUTCOME MEASURE: Pharmacists' views on generic medicines including issues surrounding efficacy, safety, quality and bioequivalence.
RESULTS: Responses were received from 219 pharmacies (response rate 15.4%). Only 50.2% of the surveyed pharmacists agreed that all products that are approved as generic equivalents can be considered therapeutically equivalent with the innovator medicines. Around 76% of respondents indicated that generic substitution of narrow therapeutic index medicines is inappropriate. The majority of the pharmacists understood that a generic medicine must contain the same amount of active ingredient (84.5%) and must be in the same dosage form as the innovator brand (71.7%). About 21% of respondents though that generic medicines are of inferior quality compared to innovator medicines. Most of the pharmacists (61.6%) disagreed that generic medicines produce more side-effects than innovator brand. Pharmacists graduated from Malaysian universities, twinning program and overseas universities were not differed significantly in their views on generic medicines. Additionally, the respondents appeared to have difficulty in ascertaining the bioequivalent status of the marketed generic products in Malaysia.
CONCLUSION: The Malaysian pharmacists' have lack of information and/or trust in the generic manufacturing and/or approval system in Malaysia. This issue should be addressed by pharmacy educators and relevant government agencies.
METHOD: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2-period crossover study with a washout period of 7 days. Paracetamol/Orphenadrine tablets were administered after a 10-h fast. Blood samples for pharmacokinetic analysis were collected at scheduled time intervals prior to and up to 72 h after dosing. Blood samples were centrifuged, and separated plasma were kept frozen (- 15 °C to - 25 °C) until analysis. Plasma concentrations of orphenadrine and paracetamol were quantified using liquid-chromatography-tandem mass spectrometer using diphenhydramine as internal standard. The pharmacokinetic parameters AUC0-∞, AUC0-t and Cmax were determined using plasma concentration time profile for both preparations. Bioequivalence was assessed according to the ASEAN guideline acceptance criteria for bioequivalence which is the 90% confidence intervals of AUC0-∞, AUC0-t and Cmax ratio must be within the range of 80.00-125.00%.
RESULTS: There were 28 healthy subjects enrolled, and 27 subjects completed this trial. There were no significant differences observed between the AUC0-∞, AUC0-t and Cmax of both test and reference preparations in fasted condition. The 90% confidence intervals for the ratio of AUC0-t (100.92-111.27%), AUC0-∞ (96.94-108.08%) and Cmax (100.11-112.50%) for orphenadrine (n = 25); and AUC0-t (94.29-101.83%), AUC0-∞ (94.77-101.68%) and Cmax (87.12-101.20%) for paracetamol (n = 27) for test preparation over reference preparation were all within acceptable bioequivalence range of 80.00-125.00%.
CONCLUSION: The test preparation is bioequivalent to the reference preparation and can be used interchangeably.
TRIAL REGISTRATION: NMRR- 17-1266-36,001; registered and approved on 12 September 2017.