Transport of phenobarbitone into the intestinal lumen and the biliary tract following i.v. administration to rats

Arimori, Kazuhiko; Nakano, Masahiro

doi:10.1111/j.2042-7158.1986.tb04595.x

Cited by 13 publications

(12 citation statements)

References 11 publications

(4 reference statements)

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“…We abstained from a longer observation time as interferences due to surgical trauma, long lasting anaesthesia and fluid loss may have influenced our results. However, compared to the known rates of gastrointestinal exsorption of intravenously administered drugs (after cannulation of the bile duct; all experiments conducted with rats) reported to be about 6% for phenobarbitone [12], 2.5% for phenytoin [8], 17% for disopyraimde [5], 1% for furosemide [7], 12% for theophylline [11], 0.4% for insecticide organophosphates [29] and 7% for acetaminophen [14], the observed amount of 3 -6% is in a comparable range.…”

Section: Discussionmentioning

confidence: 90%

Seromucosal Transport of Intravenously Administered Carbamazepine Is Not Enhanced by Oral Doses of Activated Charcoal in Rats

Eyer¹,

Jung²,

Neuberger³

et al. 2008

Basic Clin Pharma Tox

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Abstract:The fate of carbamazepine after intravenous injection in rats (n = 24) and the influence of activated charcoal on the kinetics was investigated. After randomization to four groups (n = 6, each), plasma concentration and the quantities of carbamazepine and metabolites excreted into bile, urine and intestine were determined using an in situ perfusion model of the small intestine (Ringer's solution) with or without orally administered activated charcoal (AC + ; AC-) and with or without bile duct cannulation (BD + ; BD -). The cumulative amount of carbamazepine and metabolites exsorbed into the small intestine within 3.5 hr after intravenous injection was about 15% in BD -animals and about 3% in BD + animals. About 20% of the dose was detected in the externalized bile. Activated charcoal did not influence the amount exsorbed into the small intestine. Terminal half-life in plasma ranged from 159 min. to 194 min. within the four treatment groups without statistical significant difference (P = 0.751). Correspondingly, the area under the curve did not vary significantly and ranged between 1.13 and 1.41 g/min./l (P = 0.378). Excretion of carbamazepine and metabolites into urine varied between 3% and 6% of dose within all groups and showed close correlation with diuresis. In an identical experimental approach using a 2-fold intestinal perfusion rate (50 ml/hr; n = 8), no fundamental changes compared to the main experiment regarding pharmacokinetics of carbamazepine were observed. The lack of effect of activated charcoal on the elimination of carbamazepine and metabolites must be contributed to the small amount of the drug being exsorbed into the intestine and may be further influenced by reduced intestinal permeability of carbamazepine and metabolites or inadequate luminal stirring.Activated charcoal is a widely used and generally accepted agent to prevent the absorption of orally ingested drugs, especially in the overdose setting. Although there are no satisfactorily designed clinical studies assessing the benefit from single-dose activated charcoal to recommend this therapy [1], data from literature clearly support the use of multipledose activated charcoal for some toxins such as carbamazepine, dapson, phenobarbital, quinine and theophylline in the case of overdose [2]. Besides the prevention of drug absorption and the possibility of activated charcoal interrupting the enteroenteric circulation, oral administration has also been demonstrated to enhance the clearance of intravenously administered drugs that are exsorbed seromucosally into the intestinal lumen in rats [3][4][5][6][7][8][9][10][11][12]. This process is generally called 'gastrointestinal dialysis' since it was first described in 1982 [13]. Basic pharmacokinetic requirements for clinically relevant seromucosal transport include small size of molecule, intermediate lipophilicity, low protein binding and a small volume of distribution.If a relevant amount of drug would be exsorbed into the intestinal lumen and if orally administered activated charcoa...

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Section: Discussionmentioning

confidence: 90%

Seromucosal Transport of Intravenously Administered Carbamazepine Is Not Enhanced by Oral Doses of Activated Charcoal in Rats

Eyer¹,

Jung²,

Neuberger³

et al. 2008

Basic Clin Pharma Tox

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“…However, compared to the known rates of gastrointestinal exsorption of intravenously administered drugs (after cannulation of the bile duct; all experiments conducted with rats), reported to be about 6% for phenobarbitone [2], about 2.5% for phenytoin [3], about 17% for disopyraimde [4], about 1% for furosemide [5], about 12% for theophylline [7] and 0.4% for insecticide organophosphates [22], the observed amount of 7% is in a comparable range and not negligible. It must be considered that the differences in exsorption of drugs are dependent on their individual clearance, pH of the irrigation solution, extent of protein binding, and volume of distribution, thus direct comparison of exsorption rates for different drugs is not possible offhand.…”

Section: Excretion Of Aap/m Into Bile Intestinal Lumen and Urinementioning

confidence: 85%

“…The experiment was performed using an approach similarly described by Arimori et al [2][3][4][5][6][7] with minor modifications. First, activity was counted directly in the samples by combustion and detection of liberated 14 CO 2 .…”

Section: Discussionmentioning

confidence: 99%

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Enteral Exsorption of Acetaminophen after Intravenous Injection in Rats: Influence of Activated Charcoal on This Clearance Path

Eyer¹,

Jung²,

Neuberger³

et al. 2007

Basic Clin Pharma Tox

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Abstract:The fate of acetaminophen after intravenous injection in whole bowel-irrigated rats (n = 40) and the influence of activated charcoal on the kinetics were investigated. After randomization to four groups (n = 10, each group), plasma concentration and the quantities of acetaminophen and metabolites excreted into bile, urine and intestine were determined using an in vivo model with or without orally administered activated charcoal and with or without bile duct cannulation. The cumulative amount of acetaminiphen and metabolites exsorbed into the small intestine within 3.5 hr after intravenous injection was about 20% of dose in the animals with bile duct cannulation and about 7% of dose in the animals without. Correspondingly, about 13% of dose was detected in the externalized bile. Activated charcoal did not influence the amount exsorbed into the small intestine. Terminal half-life in plasma ranged from 35 to 51 min. within the four treatment groups without statistically significant difference (P = 0.152). Correspondingly, the area under the curve did not vary much and ranged between 2.6 and 3.3 g/min./l (P = 0.392). Deposition of acetaminophen and metabolites in liver and kidney after 3.5 hr was marginal and ranged between 0.02% and 0.6% of the dose within all groups. The excretion of acetaminophen and metabolites into urine varied strikingly between 31% and 56% of the dose within all groups and correlated with diuresis. The lack of effect of activated charcoal on the elimination of acetaminophen and metabolites may be due to the small amount of the drug being exsorbed into the intestine or the reduced adsorbent capacity of activated charcoal to acetaminophen and metabolites, which also could be influenced by inadequate luminal stirring.

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“…If the fate of gentamicin in man and rabbit is similar, adsorption of small amounts of gentamicin secreted in the small intestine via bile, cannot explain the observed 40% increase in gentamicin clearance. It is likely that activated charcoal's effect on the kinetics of intravenously administered gentamicin is by adsorbing drug that has crossed the bowel wall from the mesenteric vessels, a mechanism by which oral charcoal enhances the systemic elimination of phenobarbitone (Arimori & Nakano 1986) and theophylline (McKinnon et al 1987).…”

Section: Eflect Of Activated Charcoal In Rf Rabbitsmentioning

confidence: 99%

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

Hasan

El–Sayed

Abdelaziz

1990

Journal of Pharmacy and Pharmacology

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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.

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Transport of phenobarbitone into the intestinal lumen and the biliary tract following i.v. administration to rats

Cited by 13 publications

References 11 publications

Seromucosal Transport of Intravenously Administered Carbamazepine Is Not Enhanced by Oral Doses of Activated Charcoal in Rats

Seromucosal Transport of Intravenously Administered Carbamazepine Is Not Enhanced by Oral Doses of Activated Charcoal in Rats

Enteral Exsorption of Acetaminophen after Intravenous Injection in Rats: Influence of Activated Charcoal on This Clearance Path

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

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