Single-Dose Bioequivalence Assessment of Two Formulations of Polysaccharide Iron Complex Capsules in Healthy Adult Male Chinese Volunteers: A Sequence-Randomized, Double-Blind, Two-Way Crossover Study

BACKGROUND: Iron deficiency anemia (IDA) is a common nutritional disease worldwide. Iron Supplementation is an efficient method for treating patients with IDA. Polysaccharide iron complex is an oral iron supplement that is associated with generally good tolerability and good bioavailability. OBJECTIVE: The aim of this Study was to evaluate the bioequivalence of 2 branded formulations of polysaccharide iron complex in healthy adult male Chinese Volunteers by determining the pharmacokinetic parameters after single-dose oral administration. METHODS: This sequence-randomized, double-blind, 2-way crossover Study was carried out in the Affiliated Hospital, Institute of Medical Sciences of Qingdao University, Qingdao, China. Healthy adult male Chinese volunteers were enrolled and evenly randomized to receive I of 2 formulations on day L Subjects received an oral dose of 150 mg (1 capsule) of polysaccharide iron complex with 150 mL of warm water in the morning. Capsules were of similar size, shape, and color to ensure blinding. Four hours after administration, the subjects were given standardized meals. After a 1-week washout period, the subjects were crossed over to receive the other formulation in a similar manner. The serum iron concentration 12 hours after study drug administration was determined using atomic-absorption spectrometry. The pharmacokinetic parameters C-max, T-max, AUC(0-t), and AUC(0-infinity) were obtained and analyzed using the Schuirmann 2 one-sided t test. The 2 formulations were considered bioequivalent if the test/reference ratios of C-max, AUC(0-t), and their 90% CIs were within the range of 70% to 143% for C-max and within 80% to 125% for AUC(0-t). Tolerability was monitored by Inquiring whether the subjects had experienced adverse events (AEs), with a focus on gastrointestinal AEs, during the clinic visits during the 24-hour period after drug administration and subsequently via telephone throughout the Study. RESULTS: Thirty adult male Chinese volunteers were assessed for inclusion. Twenty healthy male volunteers (10 in each group) (mean [SD] age, 21.5 [2.9] years [range, 19-23 years); weight, 66.2 [5.8] kg [range, 56-80 kg); height, 172.5 [5.1] cm [range, 162-180 cm]) were enrolled and completed the study. The pharmacokinetic parameters of the rest and reference formulations were as follows: AUC(0-t), 6.58 (2.09) and 6.58 (1.91) mu g/mL . h(-1); C-max, 1.10 (0.28) and 1.07 (0.25) mu g/mL; T-max, 3.93 (0.37) and 3.93 (0.37) hours; t(1/2), 8.33 (0.36) and 8.38 (0.41) hours; and AUC(0-infinity), 6.93 (2.23) and 6.95 (2.13) mu g/mL . h(-1), respectively. There were no statistically significant differences in AUC(0-t) or T-max by formulation, period, or subject between the test and reference formulations. Similarly, there were no statistically significant differences in C-max, by period; however, a significant difference was found in C-max by formulation (P = 0.012). No clinically significant AEs were reported with either formulation. CONCLUSIONS: In these healthy adult male Chinese volunteers, the test formulation of polysaccharide iron complex was found to be bioequivalent to the reference formulation according to the Chinese regulatory definition. A significant difference by formulation was found in C-max. The sample size was smaller than that recommended by the US Food and Drug Administration for a bioequivalence Study, and additional studies with larger sample sizes are needed. (Carr Ther Res Clin Exp. 2009;70:104-115) (C) 2009 Excerpta Medica Inc.