The study of systemic exposition of 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide in blood on rats

Introduction: The 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide (ODASA) is new antiglaucoma drug. The compounds similar in structure are able to accumulate in red blood cells. Therefore, it is necessary to evaluate the pharmacokinetic parameters of ODASA and its metabolite in whole blood of laboratory animals. Aim: Calculation of pharmacokineticparameters of ODASA and its metabolites in rat whole blood after ocular instillation andintraperitoneal injection of the drug. Materials and Methods: The 1% ocular suspension of ODASA was instilled into each eye in a volume of 20 µL to a group of 6 Wistar rats. The drug was also administrated by intraperitoneal injection at a dose of 1.6 mg/kg to another group of 6 Wistar rats. Sampling was carried out before administration and at 16 points for 288 hours after administration. HPLC-MS/MS was used for quantification of ODASA and its metabolites 4-[5-(hydroxymethyl)-1,3,4-oxadiazole-2-yl]-benzenesulfonamide (M1) and N-hydroxy-4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide (M2). Results: The high concentration level of ODASA and M1 was observed: maximum blood concentration (Cmax) of ODASA after eye instillation was 10326±532 ng/mL, Cmax of M1 was 3722±505 ng/mL(M±SEM). The Cmax value of M2 was lower – 49.9±9.4 ng/mL (M±SEM). The half-life time of the studied compounds was more than 69 h. M1 has the greatest affinity for red blood cells. The value of the area under the “concentration-time” curve (AUC0-t) of M1 in bloodwas more than 150 times higher than AUC0-t of M1 in plasma. Conclusion: The ODASA and its metabolites have long half-life time and high exposition in blood in comparison with that in plasma, which proves their accumulation in red blood cells.