The Effect of Oral Activated Charcoal on the Systemic Clearance of Gentamicin in Rabbits with Acute Renal Failure

Abstract

The effect of oral administration of activated charcoal on total body clearance of gentamicin administered intravenously (2 mg kg-1) has been studied in normal rabbits and rabbits with induced renal failure. Gastric intubation of a single dose (10 g) of activated charcoal to normal rabbits produced a significant reduction in gentamicin serum concentrations compared to control. Significant differences between treated and control groups, compatible with enhancement of gentamicin elimination, were observed in the calculated pharmacokinetic parameters (Kel, t 1/2, CL and AUC). To examine whether renal failure could augment the effect of activated charcoal in enhancing the systemic clearance of gentamicin, uranyl nitrate was used (0.75 mg kg-1, i.v.) to induce acute renal failure in rabbits. The derived pharmacokinetic parameters of gentamicin during the control phase in these animals were consistent with severe renal failure. The administration of activated charcoal, 2.5 h following gentamicin injection, produced a steeper decline in gentamicin concentration-time profiles and significant changes in Kel, t 1/2 and CL. The Kel and CL values increased to about 200%, while the t 1/2 value decreased to about 50%. The apparent changes in the pharmacokinetic parameters induced by charcoal administration were more marked in rabbits with renal failure than in normal rabbits; however, induction of renal failure did not augment the charcoal-induced clearance of gentamicin quantitatively.

Oral Activated Charcoal Prevents Experimental Cerebral Malaria in Mice and in a Randomized Controlled Clinical Trial in Man Did Not Interfere with the Pharmacokinetics of Parenteral Artesunate

“…Indeed, further exploration of the potential benefits of oAC as adjuvant treatment have to take into account that oAC is officially recommended to treat intoxication with quinine [40], increasing the elimination of this drug [24]–[26]. However, it was unknown whether the pharmacokinetics of AS, a drug now regarded to be superior to quinine for the treatment of severe malaria [14] and known to have a high endogenous clearance rate [41], would be affected by co-administration of oAC. We found no evidence of reduced plasma levels of AS or DHA due to oAC, when given simultaneously with AS, or when administered 1 h later.…”

Gastrointestinal Dialysis of Digoxin Using Cholestyramine

“…Taken together, these findings, indicate that although digoxin may not undergo significant enterohepatic circulation, it is still available for adsorption by substances like activated charcoal and binding resins and thus, could be removed by gastrointestinal dialysis. It has been shown that activated charcoal is more effective in clearing digoxin in patients with renal failure (Park et al 1985) and gentamicin in rabbits with induced renal failure (Hasan et al 1990b). The explanation for this was based on the fact that the percent increase in digoxin clearance due to activated charcoal increases as the endogenous clearance decreases.…”

“…This term came to emphasize the haemopurification effect associated with this technique similar to other processes like haemodialysis, peritoneal dialysis and haemoperfusion. Since its introduction, gastrointestinal dialysis with activated charcoal has been proven to be effective in enhancing systemic clearance of many drugs including digitoxin (Pond et al 1981), methotrexate (Gadgill et al 1982), phenobarbital (Berg et al 1982), dapsone (Neuvonen et al 1983), digoxin (Boldy et al 1985), quinidine (Hasan et al 1990a) and gentamicin (Hasan et al 1990b). By adsorbing drugs secreted into the lumen of the gastrointestinal tract, activated charcoal is proposed to set up a concentration gradient that enhances drug secretion (Levy 1982;Pond 1986).…”