Lack of effect of cimetidine and ranitidine on pyrazinamide kinetics in rats

ABSTRACT

Pyrazinamide [25 mgkg-1] kinetics was determined in cimetidine [40 mgkg-1] or ranitidine [50 mgkg-1] pretreated rats for seven days. animals received either 0.9% NaCl solution [control] or cimetidine or raintidine orally [5 mlkg-1]. Disposition of pyrazinamide was studied 24 h after the last does of pretreatment by injecting pyrazinamide [1 mlkg-1] into the tail vein. Blood samples [0.25ml] were drawn at 15.35.45 min. and 1.0, 1.5, 2.0, 3, 4, 5, 6 and 8h respectively after iv administration. Pyrazinamide plasma concentrations were analyzed using HPLC method. Cimetidine and ranitidine had no significant effect on volume of distribution [Vd], half life [t0.5], clearance [CL], mean residence times [MRT] and area under the curves [AUC] of pyrazinamide. These results suggest that cimetidine and ranitidine pretreatment does not affect significantly pyrazinamide kinetics in rats