The Safety and Tolerability of Lumbrokinase DLBS1033 in Healthy Adult Subjects.

BACKGROUND: This study was aimed to evaluate the safety and tolerability of Lumbrokinase DLBS1033 in healthy adult subjects. METHODS: This was a 2-arm, randomized, double-blind, placebo-controlled, cross-over study over 14 days of treatment with DLBS1033 490 mg 3 times daily. Eligible subjects were enrolled at Period 1 and allocated to receive either test drug or placebo, and underwent a clinical assessment including vital signs, electrocardiography, laboratory examination (hemostasis parameters, routine hematology, liver and renal function), the presence of hemorrhagic symptoms and allergic reactions. Afterwards, they went on to a 2-week washout period, and then were crossed-over to receive the alternate drug at Period 2. The procedure of Period 1 was repeated in the same manner with the alternate drug at Period 2. RESULTS: Of 20 subjects enrolled, one subject was lost to follow-up on Evaluation Day-14 of Period 2. Bleeding risk was relatively low as demonstrated by insignificant differences in hemostasis parameters between DLBS1033 and Placebo. Neither were there significant differences between DLBS1033 and Placebo in terms of hematological parameter, each blood chemistry parameter (liver function, renal function, lipid profile, fasting blood glucose), abnormality proportions of urine test, stool occult blood, and ECG interpretation. There were no hemorrhagic symptoms (petechiae, epistaxis, hematoma) and allergic reactions encountered by study subjects during the treatment with DLBS1033 and Placebo. MAJOR CONCLUSION: DLBS1033 given at the dose of 490 mg 3 times daily was safe and tolerable in healthy adults.

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.

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.