Arini Setiawati

Pharmacokinetic and Pharmacodynamic Properties of Controlled Release (CR/ZOK) Metoprolol in Healthy Oriental Subjects: A Comparison with Conventional Formulations of Metoprolol and Atenolol

The steady state pharmacokinetics and pharmacodynamics of metoprolol controlled release tablets 100 mg CR/ZOK, was compared with those of metoprolol conventional tablets 100 mg (CT) and atenolol 50 mg (ATL) in ten healthy Oriental men. The study was of double‐blind, cross‐over placebo controlled design. The three study drugs and placebo were given in a random order once daily for 4 consecutive days with 1‐week wash‐out between each period. Treadmill exercise tests were performed and blood samples were obtained at fixed intervals after the fourth dose of each treatment.

Bioequivalence study of two clopidogrel film-coated tablet formulations in healthy volunteers

The present study was performed to compare the bioavailability of two clopidogrel 75 mg film-coated tablet formulations (test formulation and reference formulation). This study was a randomized, single-blind, two-period, two-sequence cross-over study which included 24 healthy adult male and female subjects under fasting condition. The pharmacokinetic parameters were assessed based on the concentrations of clopidogrel (CAS 120202-66-6) parent compound. In each of the two study periods (separated by a washout of one week) a single dose of test or reference drug was administered. Plasma concentrations of the drug were determined by LC-MS/MS method. The pharmacokinetic parameters assessed in this study were area under the plasma concentration-time curve from time zero to 24 h (AUCt), area under the plasma concentration-time curve from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve the peak plasma concentration (t(max)), and the elimination half life (t1/2). The geometric mean ratios (90% CI) of the test drug/reference drug for clopidogrel parent compound were 95.19% (81.63-110.90%) for AUCt, 95.55% (80.50-113.42%) for AUCinf, and 100.18% (80.87-124.09%) for Cmax. The 90% confidence intervals calculated for AUCt and Cmax of clopidogrel parent compound were within the standard bioequivalence range (80-125% for AUC and Cmax). It was concluded that the two clopidogrel film-coated tablets (test and reference drug) were bioequivalent in terms of the rate and extent of absorption.

Bioequivalence study of two formulations of bisoprolol fumarate film-coated tablets in healthy subjects

Background The present study was conducted to compare the bioavailability of two bisoprolol fumarate 5 mg film-coated tablet formulations (test and reference formulations). Patients and methods This 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). Results The 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. Conclusion It 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.

Bioequivalence study of two perindopril erbumine tablet formulations in healthy volunteers.

The present study was performed to compare the bioavailability of two perindopril erbumine (CAS 107133-36-8) 4 mg tablet formulations (test formulation and reference formulation). This study was a randomized, single-blind, two-period, two-sequence cross-over study which included 20 healthy adult male and female subjects under fasting conditions. In this study, one subject withdrew from the study and one reserve subject did not appear at both periods. The pharmacokinetic parameters were assessed based on the concentrations of perindopril (CAS 82834-16-0) and perindoprilat (CAS 95153-31-4) because perindopril has litte pharmacologic activity until hydrolized in the liver into its active metabolite, perindoprilat. The blood samples from 18 subjects were analyzed for plasma concentrations of perindopril and perindoprilat. In each of the two study periods (separated by a washout of three weeks) a single dose of test or reference drug was administered. Plasma concentrations of the drug were determined by LC-MS/MS method. The pharmacokinetic parameters assessed in this study were area under the plasma concentration-time curve from time zero to 192 h (AUC), area under the plasma concentration-time curve from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax time needed to achieve the peak plasma concentration (tmax), and the elimination half-life (t(1/2)). The geometric mean ratios (90% CI) of the test drug/reference drug for perindopril and perindoprilat were 106.59% (92.97-122.20%) and 100.56% (94.11-107.46%) for AUC,, 106.64% (93.39-121.77%) and 100.88% (95.30-106.80%) for AUCinfo, and 101.23% (87.39-117.27%) and 99.30% (90.42-109.05%) for Cmax, respectively. The 90% confidence intervals calculated for AUCt and Cmax of perindopril and perindoprilat were within the standard bioequivalence range (80-125% for AUC and Cmax). It was concluded that the two perindopril erbumine tablets (test and reference drug) were bioequivalent in terms of the rate and extent of absorption.

Bioequivalence study of two risedronate sodium film-coated tablet formulations in healthy volunteers.

The present study was performed to compare the bioavailability of 2 risedronate sodium 35 mg film-coated tablet formulations (test formulation and reference formulation). Prior to the present study, in vitro comparative dissolution test has been conducted for test and reference formulations. Dissolution profiles shown that more than 85% of the drug is dissolved within 15 min at pH 1.2, pH 4.5, and pH 6.8.This study was a randomized, single-blind, 2-period, 2-sequence cross-over study which included 48 evaluable healthy adult male and female subjects under fasting condition. In each of the 2 study periods (separated by a washout of 3 weeks) a single dose of test or reference drug was administered. The pharmacokinetic parameters assessed in this study were cumulative urinary excretion from drug administration to 72 h (Ae72h) and maximum urine excretion rate (dAe/dtmax). These parameters were determined from urine concentrations of risedronate and urine volume. Urinary concentrations of the drug were determined by high performance liquid chromatographic method with UV detector.The geometric mean ratios (90% CI) of the test drug/reference drug for risedronate were 106.60% (92.34-123.07%) for Ae72h and 104.75% (88.86-123.47%) for dA/dtmax. The geometric mean ratios calculated for Ae72h and dA/dtmax of risedronate were within the bioequivalence range (80.00-125.00% for Ae72h and dA/dtmax). It was concluded that the 2 risedronate sodium film-coated tablets (test and reference drugs) were bioequivalent.

Pharmacokinetic equivalence study of nonsteroidal anti-inflammatory drug etoricoxib

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.

Bioequivalence study of 2 formulations of film-coated tablets containing a fixed dose combination of bisoprolol fumarate 5 mg and hydrochlorothiazide 6.25 mg in healthy subjects.

BACKGROUND The present study was conducted to compare the bioavailability of 2 formulations of fixed-dose combination of bisoprolol fumarate 5 mg and hydrochlorotiazide (HCT) 6.25 mg film-coated tablet (test and reference formulations). METHODS This study was a randomized, single-blind, 2-period, 2-sequence cross-over study which included 18 healthy adult male and female subjects under fasting condition. The pharmacokinetic parameters, AUCt, AUCinf, Cmax, tmax, and t½ were determined based on the concentrations of bisoprolol (CAS 66722-44-9) and HCT (CAS 58-93-5), using ultra-performance liquid chromatography with tandem mass spectrometer detector (UPLC-MS/MS). In each of the 2 study periods (with a washout of 1 week) a single dose of test or reference product was administered. RESULTS The geometric mean ratios (90% CI) of the test drug/reference drug for bisoprolol were 97.22% (93.75-100.83%) for AUCt(0-48), 97.20% (93.97-100.54%) for AUCinf, and 100.36% (93.83-107.34%) for Cmax; while those for HCT were 93.22% (84.72-102.57%), 93.39% (85.43-102.10%) and 99.39% (85.45-115.61%), for AUCt(0-24), AUCinf, and Cmax, respectively. The differences between the test and reference drug products for tmax values of bisoprolol as well as t½ values of both bisoprolol and hydrochlorothiazide were not statistically significant; yet, the difference was statistically significant for the tmax values of hydrochlorothiazide. There was no adverse event encountered during this bioequivalence test. MAJOR CONCLUSION It was concluded that the 2 formulations of fixed dose combination of bisoprolol fumarate 5 mg and hydrochlorotiazide (HCT) 6.25 mg film-coated tablet (the test and reference products) were bioequivalent.