EFFECT OF PARACETAMOL ON THE RENAL CLEARANCE AND URINARY EXCRETION OF ISONIAZID
IN GOATS
T. HUSSAIN, I. JAVED, F. H. KHAN, F.
MUHAMMAD, B. ASLAM, S. AHMAD1,
I. U. JAN2, A. BASIT AND U.
TAHIR3
Department of Physiology and Pharmacology,
University
of Agriculture,
Faisalabad; 1Department
of Animal Breeding and Genetics; 2Department of Pharmacology,
NWFP, Agricultural University, Peshwar;
3Department
of Clinical Medicine and Surgery, University
of Agriculture,
Faisalabad,
Pakistan
Abstract
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.