Effect of paracetamol on pharmacokinetics of isoniazid in Teddy goats

ABSTRACT

In this study the effect of paracetamol on pharmacokinetics [PK] of isoniazid [INH] in Teddy goats was investigated. INH was administered as a single oral dose at 10 mg/kg body weight to every experimental goat. After a wash out period of 7 days, INH and paracetamol [at the rate of 15 mg/kg body weight] were given simultaneously through oral route for investigation of drug interactions. Both times, following drug administration, blood samples were collected at predetermined time intervals from the jugular vein of each animal and analyzed for INH by spectrophotometric analysis. PK parameters were calculated using two compartment open model. When used with paracetamol, the value of biological half life [t1/2beta] of INH was significantly decreased [p<0.05] from 2.391 +/- 0.216 to 2.17 +/- 3.46 hours. The value for apparent volume of distribution [Vd] was also significantly decreased [p<0.05] from 0.905 +/- 0.327 to 0.786 +/- 0.161 L/kg and total body clearance [CL] was increased insignificantly [p>0.05] from 3.59 +/- 2.03 to 4.04 +/- 2.61 mL/min/kg. Based on these results, it was concluded that dose of isoniazid should be increased when concomitantly used with paracetamol