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Pharmacokinetics of Gentamicin and its Interaction with Paracetamol after i.v. Administration in Buffalo Calves (Bubalus bubalis)

Abstract

Baxla S.L, Kumar M, Jayachandran C, Roy B.K and Kumari A

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 ?¯??­ g/ml after alone and 545.1±25.85 ?¯??­ 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 ?¯??­ g/ml respectively. Also signi fi cantly higher distribution rate constant ( ?¯??¡ ) of 1.935±0.1119 h -1 and lower distribution half life (t 1/2 ?¯??¡ ) of 0.36±0.02 hrs were observed, when gentamicin was given with paracetamol. Elimination half life (t 1/2 ?¯??¢ ) 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.

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