Effect of Paracetamol on the Renal Clearance and Urinary Excretion of Isoniazid in Goats

Effect of paracetamol on renal clearance and urinary excretion of isoniazid was investigated in eight healthy adult female goats in two phases. In the first phase, each goat was administered isoniazid orally as a single dose at the rate of 10 mg/kg body weight. A washout period of 7 days was given before the second phase in which the same dose of isoniazid was administered along with paracetamol orally at the dose rate of 15 mg /kg. In both phases, blood and urine samples were collected at various time intervals post drug administration and analyzed for isoniazid and creatinine concentrations. The value of diuresis after single administration of isoniazid was 0.084 ± 0.0056 ml/min.kg, while following concurrent administration with paracetamol it decreased to 0.058 ± 0.0067 ml/min.kg (P>0.05). Mean values for renal clearance of creatinine following single and concurrent administration of isoniazid with paracetamol were 2.52 ± 1.151 and 1.82 ± 0.098 ml/min.kg, respectively, while respective values for renal clearance of isoniazid were 1.67 ± 0.116 and 0.80 ± 0.021 ml/min.kg (P<0.01). The ratio between renal clearance of isoniazid and paracetamol remained less than one after the administration of isoniazid alone and concurrently with paracetamol, which was indicative of back diffusion of the drug. Mean values for the cumulative percent of dose of isoniazid excreted at 12 hours following administration of isoniazid alone was 56.51 ± 2.49 versus 27.19 ± 1.96 following its concurrent administration with paracetamol (P<0.05). Thus, it is evident that besides glomerular filtration, renal handling of isoniazid also involved back diffusion and active tubular secretion. It was concluded that isoniazid was reabsorbed at tubular levels following its administration with paracetamol in goats. However, paracetamol reduced GFR inducing less urinary excretion of isoniazid.