Abstract
The disposition kinetics was conducted in fi ve healthy female buffalo calves following single i.v dose (5mg/kg) of gentamicin alone and with paracetamol (40mg/kg,i.v.). The study revealed that the plasma concentrations of gentamicin were signi fi cantly higher when it was given with paracetamol as compared to alone between 0.042 to 0.333 hrs and at 24 hrs. Serum concentrations of gentamicin was detected for longer period (48 hrs) in urine in both groups of experimental animals. In case of urine drug attained its peak level at the same time interval (1.5 hrs) in both groups with the concentration of 83.42±3.14 i g/ml after alone and 545.1±25.85 i g/ml with paracetamol administration. The extrapolated zero time plasma concentrations during distribution phase (A) and theoretical zero time plasma concentrations (Cop) were signi fi cantly (p< 0.01) higher 34.48±2.35 and 39.03±2.40 i g/ml respectively. Also signi fi cantly higher distribution rate constant ( ii ) of 1.935±0.1119 h -1 and lower distribution half life (t 1/2 ii ) of 0.36±0.02 hrs were observed, when gentamicin was given with paracetamol. Elimination half life (t 1/2 i¢ ) of 6.67±0.11 hrs was not signi fi cantly higher when gentamicin was given with paracetamol. AUC (62.16±2.82 mg/L.hrs) was signi fi cantly (p< 0.05) higher while MRT (6.93±0.36hrs) was not signi fi cantly higher when gentamicin was given with paracetamol. The values of K 12 , K 21 and Kel were calculated to be 1.088±0.111 h -1 , 0.323±0.028 h -1 and 0.628±0.024 h -1 respectively when gentamicin was given concurrently with paracetamol. T~P (5.04±0.16) was signi fi cantly (p< 0.01) higher, while Vd area (0.78±0.03L/Kg) and ClB (1.35±0.06 ml/Kg/min) were not signi fi cantly higher when gentamicin was given with paracetamol. The present investigation established that both gentamicin and paracetamol interacted with altered their kinetic behaviour. The combination with paracetamol may be beni fi cial because paracetamol reduced the maintenance doses of gentamicin which may be much advantageous in the fi eld of veterinary practice in the dose of 5 mg/kg daily by systemic route and 36 hourly when given with paracetamol in urinary tract infection.
Highlights
Gentamicin, a broad spectrum aminoglycoside is widely used in infectious diseases of animals
Concentrations of the gentamicin in urine were significantly higher from 0.083 to 24 hrs when gentamicin was given with paracetamol (Figure 2)
Paracetamol influenced the kinetics of gentamicin.Serum concentrations of gentamicin were detected upto 24hrs when gentamicin was given alone and when given with paracetamol whereas gentamicin was detectable only upto 6hrs in febrile and afebrile conditions of goat @5mg\kg after i.v. administration (Ahmad et al, 1994).The plasma concentrations of gentamicin were found to be significantly higher initially (0.042 to 0.333 hrs) when it was given in combination with paracetamol as compared to its alone administration
Summary
Gentamicin, a broad spectrum aminoglycoside is widely used in infectious diseases of animals. It is used to treat various infections caused by aerobic Gram negative bacteria such as E.coli, Salmonella, Klebsiella, Proteus, Haemophilus, Pasteurella, Compylobactor and Pseudomonas. It binds to 30s ribosomal subunit; it appear to bind to several sites on the 50s ribosomal subunit. Paracetamol is effective in the central nervous system and in endothelial cells It does not affect function of platelets and clotting factors and is less gastrointestinal irritant. It is a suitable substitute for aspirin for its antipyretic or analgesic actions
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