ABSTRACT
PURPOSE: The current study aimed to evaluate whether a generic product of etoricoxib 120 mg film-coated tablet (the test drug) was bioequivalent to the reference product (Arcoxia® film-coated tablet 120 mg). METHODS: This was a randomized, open-label, two-sequence, crossover study under fasting condition, with a 14-day washout period, involving 26 healthy adult male and female subjects. Blood samples were taken and analyzed for plasma concentrations of etoricoxib (Chemical Abstracts Service [CAS] 202409-33-4) using a high-pressure liquid chromatography-ultraviolet detector (HPLC-UV) system capable of measuring etoricoxib concentrations ranging from 5.00 to 5002.90 ng/mL, with the lowest limit of quantitation of 5.00 ng/mL. A noncompartmental method was used to determine the pharmacokinetic parameters of a single-dose administration of the drug, including the area under plasma concentration-time curve from time zero to the time of last observed concentration (AUC0-t ), the area under plasma concentration-time curve from time zero to infinity (AUC0-∞), the maximum plasma concentration (Cmax), the time to reach the maximum plasma concentration (tmax), and the terminal half-life (t½). RESULTS: After a single-dose administration of etoricoxib 120 mg film-coated tablet, the mean (SD) values for the AUC0-72h and Cmax of the test drug were 45913.42 (13142.19) ng·h/mL and 3155.93 (752.81) ng/mL, respectively; the values for the reference drug were 44577.20 (13541.85) ng·h/mL and 2915.13 (772.81) ng/mL, respectively. The geometric mean ratios (90% CIs) of the test drug/reference drug were 103.40% (98.70%-108.32%) for AUC0-72h and 109.26% (100.18%-119.18%) for Cmax. No clinically significant differences in tmax and t½values were found between the test drug and the reference drug. No adverse events were experienced by the subjects during this study. CONCLUSION: The present study demonstrated that the evaluated generic etoricoxib 120 mg film-coated tablets were bioequivalent to the reference drug.
ABSTRACT
PURPOSE: The present study was conducted to evaluate whether the bioavailability of pregabalin capsules 150 mg manufactured by PT Dexa Medica was equivalent to the reference formulation. METHODS: This was a randomized, open-label, two-period, two-sequence, and crossover study under fasting condition, with a 1-week washout period. Plasma concentrations of pregabalin from 20 subjects were determined by using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) detection method. Pharmacokinetic parameters assessed in this study were: area under the plasma concentration-time curve from time zero to last observed quantifiable concentration (AUC0-t), area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), maximum plasma concentration (Cmax), time to maximum plasma concentration (tmax), and terminal half-life (t1/2). The 90% confidence intervals (CIs) for the geometric mean ratios of test formulation/reference formulation were calculated for the AUC and Cmax parameters; while tmax difference was analyzed nonparametrically on the original data using the Wilcoxon matched-pairs test, and t1/2 difference was analyzed using Student's paired t-test. RESULTS: The mean (standard deviation [SD]) AUC0-t, AUC0-∞, Cmax, and t1/2 of pregabalin from the test formulation were 27,845.86 (4,508.27) ng · h/mL, 28,311.70 (4,790.55) ng · h/mL, 3,999.71 (801.52) ng/mL, and 5.66 (1.20) hours, respectively; while the mean (SD) AUC0-t, AUC0-∞,Cmax, and t1/2 of pregabalin from the reference formulation were 27,398.12 (4,266.28) ng · h/mL, 27,904.24 (4,507.31) ng · h/mL, 3,849.50 (814.50) ng/mL, and 5.87 (1.25) hours, respectively. The median (range) tmax of pregabalin from the test formulation and reference formulation was 1.00 (0.67-2.00) hours and 1.00 (0.67-3.00) hours, respectively. The 90% CIs for the geometric mean ratios of test formulation/reference formulation for pregabalin were 101.54% (98.75%-104.41%) for AUC0-t, 101.35% (98.66%-104.11%) for AUC0-∞, and 104.19% (98.75%-109.93%) for Cmax. CONCLUSION: The study concluded that the two formulations of pregabalin capsules studied were bioequivalent.
ABSTRACT
BACKGROUND: DLBS1442, a proprietary and standardized semipolar bioactive extract of the fruit Phaleria macrocarpa, is preclinically proven to have anti-inflammatory properties. The current clinical study evaluated the efficacy and safety of DLBS1442 in alleviating symptoms of premenstrual syndrome and primary dysmenorrhea. METHODS: This was an open study over four menstrual cycles (with two control cycles, followed by two treatment cycles). Women with premenstrual syndrome and/or primary dysmenorrhea, 18-40 years of age, and with a regular menstrual cycle were included in the study. In the treatment cycles, DLBS1442 extract was given as a 100 mg capsule two or three times daily (for those with mild and moderate-to-severe baseline abdominal pain, respectively), for an average of six days, ie, three days before until the end of the first three days of the menstrual period. Throughout all four study cycles, daily self-assessment of symptoms related to premenstrual syndrome was made by each subject using a visual analog scale (VAS). Data were descriptively analyzed and profiled in curves of VAS score versus time point evaluation starting from day 5 before menstruation to day 5 of menstruation. RESULTS: Twenty-three subjects of mean age 27.35 ± 5.73 years were evaluable for the intention to treat analysis. Most subjects experienced the primary efficacy variable (abdominal pain), peaking on days 1-2 of the menstrual phase, with a mean VAS score of 36.8 ± 24.3 mm and 30.0 ± 29.6 mm, respectively, during control cycles. DLBS1442 markedly reduced VAS scores by 13.76 ± 28.27 mm (37.46%) and 13.28 ± 29.06 mm (44.28%), respectively. Other symptoms of premenstrual syndrome were also markedly alleviated by DLBS1442. Some mild adverse events were observed and resolved by the end of the study. CONCLUSION: This preliminary study indicates the effectiveness of DLBS1442 in alleviating primary dysmenorrhea and abdominal pain, as well as other symptoms related to premenstrual syndrome. DLBS1442 was safe and well tolerated in women with premenstrual syndrome and/or dysmenorrhea.
ABSTRACT
A double-blind, randomized, parallel and active-controlled clinical study was conducted to evaluate the anti-hypertensive effect as well as the tolerability of Olive leaf extract in comparison with Captopril in patients with stage-1 hypertension. Additionally, this study also investigated the hypolipidemic effects of Olive leaf extract in such patients. It consisted of a run-in period of 4 weeks continued subsequently by an 8-week treatment period. Olive (Olea europaea L.) leaf extract (EFLA(®)943) was given orally at the dose of 500 mg twice daily in a flat-dose manner throughout the 8 weeks. Captopril was given at the dosage regimen of 12.5 mg twice daily at start. After 2 weeks, if necessary, the dose of Captopril would be titrated to 25 mg twice daily, based on subject's response to treatment. The primary efficacy endpoint was reduction in systolic blood pressure (SBP) from baseline to week-8 of treatment. The secondary efficacy endpoints were SBP as well as diastolic blood pressure (DBP) changes at every time-point evaluation and lipid profile improvement. Evaluation of BP was performed every week for 8 weeks of treatment; while of lipid profile at a 4-week interval. Mean SBP at baseline was 149.3±5.58 mmHg in Olive group and 148.4±5.56 mmHg in Captopril group; and mean DBPs were 93.9±4.51 and 93.8±4.88 mmHg, respectively. After 8 weeks of treatment, both groups experienced a significant reduction of SBP as well as DBP from baseline; while such reductions were not significantly different between groups. Means of SBP reduction from baseline to the end of study were -11.5±8.5 and -13.7±7.6 mmHg in Olive and Captopril groups, respectively; and those of DBP were -4.8±5.5 and -6.4±5.2 mmHg, respectively. A significant reduction of triglyceride level was observed in Olive group, but not in Captopril group. In conclusion, Olive (Olea europaea) leaf extract, at the dosage regimen of 500 mg twice daily, was similarly effective in lowering systolic and diastolic blood pressures in subjects with stage-1 hypertension as Captopril, given at its effective dose of 12.5-25 mg twice daily.
