Abstract
The rats model has never thoroughly investigated the influence of tramadol on plasma pethidine concentration besides pethidine pharmacokinetics. Individually, analgesic ED50s for pethidine and tramadol are estimated as 3.55 and 24.21 mg/kg, i.p. Subsequently, their measures decreased to 1.65 and 11.27 mg/kg, i.p., when both were given in combination at 1:1 from ED50s. Tramadol and pethidine have a form of synergistic analgesic interaction, which is therefore classified as a pharmacodynamic interaction. Pethidine (7.1mg/kg, i.p.) reveals the plasma concentration of 369.00, 493.33, 373.33, 305.33, 306.33 and 247.67 µg/ml that was measured over distinctive times of 0.25,0.5,1,2,4, and 24 hours. At the same time, the concentration of plasma levels of tramadol and pethidine (48.42 and 7.1mg/kg, i.p., correspondingly) declined to 229.33, 268.33, 233.00, 198.33, 195.67 and 180.33 µg/ml by 38, 46, 38, 35, 36 and 27%, respectively. Tramadol affected the pethidine pharmacokinetics through an elevation in the area-under-curve (AUC0-∞) 49%, area-under-moment-curve (AUMC0-∞) 343%, mean-residence-time (MRT) 137%, half-life (t1/2β) 136%, and the distribution volume (Vss) 64%. Other estimated pharmacokinetic measures were reduced which included maximal concentration (Cmax) 47% and elimination rate constant (Kel) 60%. In general, the findings revealed a synergism as a mode of pharmacological interaction between pethidine and tramadol, in addition to a change in pethidine pharmacokinetics, which could improve pethidine effectiveness in the rat’s model.
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