ABSTRACT
This study investigated the effect of food or water deprivation on the pharmacokinetics of paracetamol in 30 Holstein-Friesian preruminant calves (10 controls, 10 food withheld and 10 water-deprived) aged 24-25 days. Control calves were given paracetamol at 24-25 days and again at 28-29 days of age. In the food withheld and water-deprived calves paracetamol studies were performed before and after 4 days of food or water deprivation. In the control group there were no significant differences in pharmacokinetic parameters for paracetamol in 24-25 and 28-29-day-old calves. Witholding food for 4 days was associated with an increase in the mean residence time (MRT) of paracetamol (P < 0.01). When food was withheld total body clearance (ClB) of paracetamol was significantly decreased (P < 0.05). The volume of distribution (Vss) was not significantly altered. Similarly, water deprivation was associated with a significant increase in MRT and significant decrease in ClB of paracetamol (P < 0.01). The Vss was not significantly altered. Food or water deprivation also influenced the formation of major metabolites (glucuronide and sulphate) of paracetamol. It is concluded that food or water deprivation may impair the elimination drugs that undergo metabolism by UDP-glucuronyltransferase and sulphotransferase in cattle.
Subject(s)
Acetaminophen/pharmacokinetics , Analgesics, Non-Narcotic/pharmacokinetics , Food Deprivation , Water Deprivation , Acetaminophen/administration & dosage , Analgesics, Non-Narcotic/administration & dosage , Animals , Cattle , Infusions, IntravenousABSTRACT
The effect of four days water deprivation on the metabolism of antipyrine was studied in female Holstein-Friesian calves, aged 24 to 25 days, by measuring the antipyrine plasma clearance and the excretion of three major metabolites of antipyrine in urine. Water deprivation was associated with a statistically significant (P < 0.01) increase in the plasma antipyrine elimination half-life from 10.85(1.14) hours to 14.00(1.05) hours. In water deprived calves the systemic clearance of antipyrine was significantly (P < 0.05) decreased from 0.75(0.07) ml min-1 kg-1 to 0.56(0.05) ml min-1 kg-1. The excretion of three major metabolites of antipyrine: 4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine in urine was significantly (P < 0.01) decreased after water deprivation. In the control group no significant differences between the pharmacokinetic parameters of antipyrine in 24 to 25 and 28 to 29 day-old calves were observed. Also urinary profiles of antipyrine in calves from the control group did not differ significantly between 24 to 25 and 28 to 29 days of life. Our data indicate that water deprivation inhibits antipyrine elimination in calves.
