Equilab International (Indonesia)

<p><strong>Background: </strong>Malaria is still considered as a major health problem in the world including in Indonesia, which is regarded as one of the malaria-endemic countries. Since 2006, WHO has recommended the use of artemisinin-based combination therapy (ACT) to treat uncomplicated falciparum malaria. In Indonesia, DHP tablet (combination of dihydroartemisinin and piperaquine) is the first line therapy used in malaria control program, which currently used imported DHP tablet. To produce generic DHP tablet, comparative bioequivalence test between DHP tablet and the drug previously used is needed. <strong>Methods: </strong>A single dosed, randomized, double-blinded, one-period, and parallel study design was conducted in the present research. Every twenty-four subjects were assigned into two groups, which are test group and comparison group. <strong>Results: </strong>The results showed that even though in vitro comparison of dissolution test has fulfilled the requirements, in vivo test results has not fulfilled the bioequivalence standards. Obtained geometric mean ratios (90% confidence intervals) of the test drug to comparator drug for dihydroartemisinin were 83.30% (67.06%–103.48%) for AUC<sub>0-t</sub>, 83.24% (67.10%–103.26%) for AUC<sub>0-inf</sub>, and 75.67% (61.83%–92.61%) for C<sub>max</sub>. The geometric mean ratios (90% confidence intervals) of the test drug to comparator drug for piperaquine were 97.31% (76.50%–123.80%) for AUC<sub>0-t</sub>, 94.18% (74.18%–119.59%) for AUC<sub>0-inf</sub>, and 96.47% (71.80%–129.62%) for C<sub>max</sub>. <strong>Conclusions: </strong>Therefore, the pharmacokinetic profile of the test drug is concluded to be bio-inequivalent with the comparator drug.</p>

PurposeThe 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).MethodsThis 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 s 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).ResultsAfter 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.ConclusionThe present study demonstrated that the evaluated generic etoricoxib 120 mg film-coated tablets were bioequivalent to the reference drug.

BackgroundThe current study was conducted to find out whether two oral preparations of 300 mg gabapentin (the test and reference capsules) were bioequivalent.Subjects and methodsThis was a randomized, single-blind, crossover study under fasting condition, with a 7-day washout period, which included 37 healthy adult male and female subjects. After an overnight fast, subjects were given, orally, one capsule of the test drug or of the reference drug. Blood samples were drawn immediately before taking the drug, then at 20 and 40 minutes, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, and 24 hours after dosing, to evaluate pharmacokinetic parameters of the single dose administration, ie, the area under the plasma concentration–time curve (AUC) from time zero to 24 hours (AUCt), AUC from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve Cmax (tmax), and the elimination half-life (t1/2). The plasma concentrations of gabapentin were determined using validated high-performance liquid chromatography with ultraviolet detection.ResultsThe geometric mean ratios (90% confidence interval) of the test drug/reference drug for gabapentin were 103.15% (90.38%–117.72%) for AUCt, 103.53% (90.78%–118.07%) for AUCinf, and 108.06% (96.32%–121.24%) for Cmax. The differences in tmax and t1/2 values between the test and reference drug products for gabapentin were not statistically significant. Light-headedness, nausea, and headache were encountered during the study, but they were all mild and well tolerated. The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of gabapentin were within the acceptance range for bioequivalence.ConclusionThe two preparations of gabapentin 300 mg capsule were bioequivalent, thus both can be used interchangeably in the clinical setting.

BackgroundThe present study was conducted to compare the bioavailability of two bisoprolol fumarate 5 mg film-coated tablet formulations (test and reference formulations).Patients and methodsThis study was a randomized, single-blind, two-period, two-sequence crossover study that included 18 healthy adult male and female subjects under fasting condition. The pharmacokinetic parameters were determined based on the concentrations of bisoprolol (CAS 66722-44-9), using ultraperformance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout of 1 week) a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration-time curve from time zero to 48 hours (AUCt), AUC from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve Cmax (tmax), and the elimination half-life (t½).ResultsThe geometric mean ratios (90% confidence intervals) of the test drug/reference drug for bisoprolol were 101.61% (96.14%–107.38%) for AUCt, 101.31% (95.66%–107.29%) for AUCinf, and 100.28% (93.90%–107.09%) for Cmax. The differences between the test and reference drug products for bisoprolol tmax and t½ values were not statistically significant (P > 0.05). There was no adverse event encountered during this bioequivalence test. The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of bisoprolol were within the acceptance range for bioequivalence.ConclusionIt was concluded that the two bisoprolol film-coated tablet formulations (the test and reference products) were bioequivalent in terms of the rate and extent of absorption.