Abstract

Purpose: The genetic makeup of each individual varies among each other and has changed the pharmacokinetics. Thus, pharmacokinetics of every region has variations, due to the changes in genetic expression of various genes. Allopurinol inhibited xanthine oxidase that declined the uric acid from body. The pattern for pharmacokinetics of allopurinol in Pakistani males was calculated and the bioequivalence was compared for two brands of allopurinol drug. Tab. Zyloric^® 300 mg, GlaxoSmith- Kline, Karachi, Pakistan was used as reference drug and Tab. Zynol^® 300 mg, Pharmedic Laboratories, Lahore, Pakistan was utilized as a test drug.

Method: A single dose per period, crossover, open label, two period study was conducted on 08 healthy adult volunteers. Sampling comprised of two study periods, each was separated by interval of 1 week. Volunteers received a single oral dose of allopurinol 300 mg on sampling day. Blood was collected at 0, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 5 and 6 hours of dose administration and blood sampling was analyzed by the HPLC method.

Results and Conclusion: The calculation of volume of distribution, elimination half life, clearance, maximum concentration of drug, time required to achieve maximum concentration, area under curve and mean residence time was determined by using pharmacokinetics software (APO). The observed Cmax was 2.44 µg/ml and T_max was calculated to be 1.33 hr, respectively. AUC calculated by trapezoidal rule was 8.62 h.µg/ml. V_d was known to be 1.32 L/kg. Clearance was amounted at 0.45 L/hr. 2.88 hr was found to be mean residence time of allopurinol inside the body. Upon calculation of bioequivalence parameters, it was sorted out that AUC (8.62:8.74 h.µg/ml; Zyloric Vs Zynol) C_max (2.44:2.50 h.µg/ml; Zyloric Vs Zynol) and T_max (1.33:1.35 h.µg/ml; Zyloric Vs Zynol) were found to be in FDA determined bioequivalence criteria. Allopurinol, oxypurinol and allopurinol riboside showed maximum binding affinity with Xanthine Oxidoreductase. Docking analyses elucidated that Ser-425, Lys-433, Gly-502, Met-504, Leu-1209, Glu-1210, Glu-1211, His-1213, Thr-1227, Thr-1228, Lys-1229, Thr- 1302, Thr-1329 are critical residues for ligand-receptor interactions.

Keywords: Allopurinol riboside, allopurinol, bioequivalence, gouts disease, in silico analyses, molecular docking studies, oxypurinol.

Graphical Abstract