Different effect of pre-treatment with phenobarbital on transintestinal elimination of moxifloxacin and ciprofloxacin: preliminary data

he fluoroquinolones (FQ) are widely used in clinical practice, andexhibit pharmacokinetic properties such as good oral bioavailability,transintestinal elimination through the gut, and biliary excretion. FQscan interfere with hepatic metabolism and drug interaction withenzyme inducers may occur. Few data are available about intestinalconcentrations of FQs and their pharmacokinetics interactions in thegastrointestinal compartement.Objectives. To study the effect of phenobarbital (Phe, enzyme inducer)on intestinal, hepatic and faecal concentrations of Moxifloxacin (Mxf)and Ciprofloxacin (Cpx).Methods. 30 Wistar rats (180.2+/-7.8 g weight, mean+SD) were dividedin 6 groups and treated as follows: group1: Phe (80 mg/kg/day, i.p.)and Mfx (10 mg/kg/day, po) 2 hours later; group 2: Phe (80 mg/kg/day,i.p.) and Mfx (50 mg/kg/day, po) 2 hours later; group 3: Phe(80 mg/kg/day, i.p.) and Cpx (15 mg/kg/day, po) 2 hours later; group4:Mfx (10 mg/kg/day, po); group 5: Mfx (50 mg/kg/day, po); group 6:Cpx (15 mg/kg/day, po). Samples of blood, intestinal and liver tissues,and faeces were collected after three days, 2 hours after the lastFQs administration. Cpx and Mxf concentrations were determined withmicrobiological method (agar diffusion, K. pneumoniae, Isosensitestagar).Results. Mfx was not detected when administered at 10 mg/kg/day;pre-treatment with Phe induced no modifications. Higher dosesof Mxf (50 mg/kg/day) produced good intestinal concentrations(10.3+/-5.5 mg/kg) that increased to 16.3+/-4.3 mg/kg in rats pretratedwith Phe. Faecal concentrations of Mfx are similar in the two treatedgroups (280.0+/-32.1 mg/Kg). Mfx was not detected in serum and hepatictissue. Cpx: Intestinal concentrations of Cpx were 10.4+/-12.2 mg/kg,when administered alone, and 24.8+/-23.7 mg/kg in rats pretreated withPhe; parallel respective serum levels showed a slight decrease(0.04 and0.02 mg/L, respectively). Cpx was detected only in liver of rats pretreatedwith Phe. Faecal concentrations of Cpx were 231.6+/-279.9 mg/kg whenadministered alone and 87.0+/-44.0 mg/kg in rats pretreated with Phe.Conclusions. The enzyme inducer Phe produced an increase of theconcentrations of Mfx and Cpx in the intestinal tissue. Mfx and Cpxshowed different behaviour in the intestinal compartment. Phe canmodify the pharmacokinetics of Cpx and, in minor extent, that of Mxf.MIUR PRIN 2003-Prot. N. 2003051858_003