Influence of experimentally induced cholestasis on the pharmacokinetics of cefotiam.

The pharmacokinetics of (7 beta-[2-(2-amino-thiazol-4-yl) acetamido]-3-[[1-(2-dimethylaminoethyl)-1H-tetrazol- 5-yl]thio)methyl)-ceph-3-em-4-carboxylic acid (cefotiam) was studied in rabbits with normal and experimentally decreased or annulled biliary excretion. The latter two states were induced by administration of 17 beta-estradiol and by tying of the choledochus, respectively. All animals included in the study received a single i.v. bolus type injection of 40 mg/kg of the antibiotic. The average values of the pharmacokinetic parameters obtained after such administration to the control rabbits, with normal biliary excretion, expressed in accordance with a two-compartment open kinetic model were: alpha = 15.598 h-1; beta = 2.717 h-1; K12 = 5.247 h-1; K21 = 7.093 h-1 and K13 = 5.975 h-1. Cholestasis modifies the parameters defining the distribution and elimination of cefotiam to a considerable extent. The serum half-life of the slow elimination phase had an average value of 0.116 h in the control group and 0.207 h in the group with mechanically induced cholestasis. Chemically induced cholestasis caused a lesser increase in the serum half-life.