Pharmacokinetics, Bioequivalence, and Safety Evaluation of Two Oral Formulations of Calcium Dobesilate Capsules in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

ABSTRACT

To determine the pharmacokinetics (PK), safety, and bioequivalence profiles of 0.5-g calcium dobesilate capsules in both fasting and fed states for the test drug and reference drug. A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier CTR202000268-01). The fasting and fed studies, both involving 24 subjects, were conducted. A single dosage of either the reference or the test preparation was given to each eligible subject in a 11 ratio, followed by a 7-day rest interval before the administration of the alternative formulation. After taking the capsules, plasma samples were taken for 48 hours, and using liquid chromatography-tandem mass spectrometry, the calcium dobesilate level was determined. The PK parameters evaluated in the study included the maximum serum concentration (Cmax), area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration, AUC from time 0 to infinity, half-life, time to Cmax, and terminal elimination rate constant. In addition, the safety evaluation encompassed monitoring fluctuations in vitals (temperature, pulse, and blood pressure) and laboratory tests (urinalysis, hepatic function, blood biochemistry, and hematology), as well as recording the emergence of adverse events (AEs). The geometric mean ratio (GMR) of the test/reference medications was used to assess bioequivalence by determining if the 90% confidence intervals of the GMR fell within the predefined range of 80%-125%. AEs were assessed as safety end points. The study included 48 healthy Chinese volunteers (with n = 24 each for the fasting and the fed conditions), and no subjects dropped out for any reason. The differences in the PK metrics for the test and reference drugs for both conditions were insignificant (P > .05). For bioequivalence, irrespective of whether the food was consumed or not, the range of the 90% confidence intervals of the GMR for Cmax, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity was between 80% and 125%. In the experiment, no serious AEs were recorded. Our findings revealed that the calcium dobesilate capsules used as the reference and the test drugs were both bioequivalent. Irrespective of whether the healthy Chinese volunteers consumed food or not, the PK and safety profiles were comparable.