Effects of activated charcoal and sorbitol on sodium pentobarbital absorption in the rat

Three activated charcoals were tested for their ability to reduce the oral absorption of sodium pentobarbital (SP) in rats. Fasted adult, male rats were given 40 mg/kg of C-14 labelled SP by gavage (2 ml). Five minutes after drug administration, the animals were given 40 mg of either Darco (G-60), United States Pharmacopeia (USP) or SuperChar (SC) activated charcoals. The charcoals were administered as a slurry in either 1 ml of water, or 1 ml of 70 percent (w/v) sorbitol solution. Water (control) and sorbitol given alone were tested separately. Various pharmacokinetic parameters were calculated from the plasma concentration of SP determined at various time intervals after drug administration. When given in water, only SC significantly (p less than .01) reduced the peak plasma concentration and oral bioavailability of SP. Sorbitol given alone produced diarrhea but did not affect drug absorption. However, sorbitol selectively enhanced the effectiveness of G-60 and USP charcoals and, as a result, all charcoals significantly reduced SP absorption when given along with the cathartic. The results suggest that when given in water, charcoal antidotal effectiveness is proportional to absorptive surface area, and that sorbitol may enhance the antidotal effectiveness of some charcoals but not others.     

Ferrous sulfate adsorption by activated charcoal

Although activated charcoal is thought to not appreciably adsorb iron salts, previous in vitro work indicates some adsorption of iron. This study characterized the adsorptive capacity of activated charcoal for ferrous sulfate at 3 pH environments. Langmuir adsorption isotherms were determined with a fixed amount of iron in the reaction vessels. Activated charcoal USP (20, 40, 60, 80, 100, or 120 mg) was placed in plastic tubes to which were added 1 of 3 different simulated gastrointestinal fluids (pH = 1.5, 4.5, or 7.5) and 1.49% ferrous sulfate in water. The reaction vessels were agitated and immersed in a water bath at 37 C for 30 min. Each series was performed in triplicate. Following temperature eQuilibration filtration yielded an aliquot that was assayed for iron by atomic absorption spectrophotometry. Adsorptive capacities (mean +/- SD) of activated charcoal for ferrous sulfate (mg elemental iron/g charcoal) at pH 4.5 (102.96+/-4.49) and pH 7.5 (100.94+/-19.02) were higher (P<0.01) than at pH 1.5 (-0.01+/-0.26). At pH 1.5 iron was not appreciably adsorbed by activated charcoal. Activated charcoal adsorbed ferrous sulfate to a greater extent at pH environments where iron is typically absorbed from the gastrointestinal tract. These results indicate that activated charcoal may prove an effective therapy for acute iron poisoning and further investigation is warranted.     

Decreased absorption of propoxyphene by activated charcoal

In 1968 we first suggested that activated charcoal (AC) should be administered in the emergency treatment of propoxyphene overdosage. The dramatic increase in recent years of deaths involving propoxyphene has prompted us to again evaluate the efficacy of AC in preventing absorption of propoxyphene from the GI tract. Male rats (100-125 g) were administered propoxyphene hydrochloride (P-HCl, 350 mg/kg) or propoxyphene napsylate (P-N, 825 mg/kg) either dissolved or suspended in 5% acacia in H2O. After 30 min the rats were administered either AC at 10 times the drug dose or water. Surviving rats were sacrificed at 1, 2, 4, 8, 12, and 24 h; the brain, liver, and both kidneys were removed intact, weighed, and stored at -70 degrees C. After lyophilization, the tissues were analyzed for propoxyphene and its metabolite, norpropoxyphene, by GLC. There were significantly less deaths in rats that received P-HCl + AC or P-N + AC than rats that received either P-HCl or P-N alone (9 vs 19, p less than .01 and 5 vs 10, p less than .05 respectively). Tissue levels of propoxyphene and norpropoxyphene were similarly significantly reduced. These studies provide further evidence of the efficacy of AC in propoxyphene overdosage.     

In vitro adsorption of sodium pentobarbital by SuperChar, USP and Darco G-60 activated charcoals

This study was designed to examine the in vitro adsorption of sodium pentobarbital by three activated charcoals. Solutions of sodium pentobarbital (20 mM) were prepared in distilled water and in 70% sorbitol (w/v). Radiolabeled (14C) sodium pentobarbital was added to each solution to serve as a concentration marker. Two ml of each drug solution was added to test tubes containing 40 mg of either Darco G-60, USP, or SuperChar activated charcoal. The drug-charcoal mixtures were incubated at 37 degrees C for O, 2.5, 5, 7.5 or 10 min. Equilibrium, indicated by a constant percentage of drug bound for two consecutive time periods, was established immediately for the aqueous mixtures and for Darco G-60 in sorbitol. The time to equilibrium was prolonged for USP (2.5 min) and SuperChar (5 min) in the presence of sorbitol. In the second series of experiments, solutions of sodium pentobarbital (1.25 to 160 mM) were prepared in either distilled water or sorbitol. Amount of drug bound by 10 to 320 mg of activated charcoal within a 10 min incubation period was determined. Scatchard analysis determined maximum binding capacity (Bmax) and dissociation constants (Kd) for each activated charcoal. In water, Bmax (mumoles/gm) was greatest for SuperChar (1141), followed by USP (580) and Darco G-60 (381), while the Kd's did not differ. Sorbitol did not change the Bmax or Kd of USP or Darco G-60, but the additive significantly decreased the Bmax (717) and increased the Kd for SuperChar (3.3 to 10.1 mM). The results suggest that relative binding capacity of activated charcoal is directly proportional to surface area, and that sorbitol significantly reduces sodium pentobarbital binding to SuperChar.     

Comparative efficacy of thallium adsorption by activated charcoal, prussian blue, and sodium polystyrene sulfonate

BACKGROUND: Although Prussian blue is considered the antidote of choice for thallium poisoning, the lack of a Food and Drug Administration-approved pharmaceutical formulation has led to the search for other adsorbents. Activated charcoal has been demonstrated to adsorb thallium in vitro, and the similarity between thallium and potassium has led some authors to consider the use of sodium polystyrene sulfonate as a potential adsorbent. This experiment was designed to compare the relative thallium binding efficacy of these agents in a standard isotherm model. METHODS: A standard aqueous solution of thallium acetate buffered to pH 7.0 was agitated at 25 degrees C with activated charcoal, Prussian blue, or sodium polystyrene sulfonate at adsorbent:thallium ratios ranging from 1.5:1 to 100:1. In order to further simulate physiologic conditions, all trials were repeated in a solution containing 4 mmol/L potassium phosphate. After thorough agitation, the mixtures were allowed to settle and were centrifuged and filtered through a 0.22-micron filter. Supernatant thallium concentrations were measured by atomic absorption spectrophotometry. Langmuir isotherms were used to calculate the maximal adsorptive capacity of each adsorbent, using linear regression with Pearson's correlation coefficients (r). Maximal adsorptive capacities were compared statistically with a p < 0.05 considered significant. RESULTS: The maximal adsorptive capacities defined as milligrams of thallium per gram of adsorbent (shown with linear regression p and r values) were as follows: activated charcoal, 59.7 mg/g (p = 0.005, r = 0.995); Prussian blue, 72.7 mg/g (p = 0.004, r = 0.996); and sodium polystyrene sulfonate, 713 mg/g (p = 0.049, r = 0.951). All three values were statistically different from each other. At a physiologic potassium concentration, the maximal adsorptive capacities for activated charcoal and Prussian blue were essentially unchanged (58.3 mg/g and 69.8 mg/g, respectively, p > 0.05 for each vs trials without potassium), while the maximal adsorptive capacity for sodium polystyrene sulfonate fell to 39.1 mg/g (p = 0.003, r = 0.997, p = 0.005 vs sodium polystyrene sulfonate without potassium). CONCLUSIONS: This in vitro study confirms the utility of Prussian blue and activated charcoal as thallium adsorbents. Although sodium polystyrene sulfonate demonstrates exceptional in vitro adsorption of thallium, its greater affinity for potassium probably renders it clinically ineffective.     

Adsorptive capacity of activated charcoal for rifampicin with and without sodium chloride and sodium citrate.

The effects of two saline cathartics (sodium chloride and sodium citrate) on the adsorptive capacity of activated charcoal (AC) for rifampicin were studied. Solutions of rifampicin alone and rifampicin with 7.5 mg/ml cathartic solution were vortex-mixed for 30 s with different quantities of AC. These were incubated for 30 min at 37 degrees C and analyzed for free rifampicin spectrophotometrically at 320 nm. The addition of sodium citrate significantly increased (p<0.05) the adsorptive capacity of AC for rifampicin with a resulting decrease in B-50 values at both the therapeutic and simulated toxic doses. Sodium chloride addition reduced the binding of rifampicin to AC at the toxic doses. The adsorption of rifampicin to activated charcoal, both alone and with the two saline cathartics, obeyed quantity-dependent kinetics. AC may be co-administered with sodium citrate in the management of rifampicin overdose.     

Modulation of conditioned taste aversion by sodium pentobarbital

The effects of pentobarbital on the formation and expression of LiCl induced taste aversion were examined using a two-bottle preference test. Rats adapted to restricted fluid intake were offered a 15% sucrose solution 15 min after a pentobarbital or saline injection but prior to post-CS LiCl or control injections. All animals were tested 3 days later in either the same or opposite drug state, and were returned to the conditioning day drug state for a second test. The results showed that pentobarbital in testing disrupted evidence for taste aversion in a manner not simply accounted for by its dipsogenic effects. It was suggested that the present paradigm may prove to be a simple behavioral assay for screening putative anxiolytic drugs.     

Prevention of chloroquine absorption by activated charcoal.

1. The ability of activated charcoal to prevent the absorption of chloroquine was investigated in healthy volunteers, and the effect of the charcoal-chloroquine ratio on the completeness of binding was studied in vitro. 2. After an overnight fast, six subjects ingested 500 mg of chloroquine phosphate with water, and another group of six subjects ingested 25 g of charcoal suspension within 5 min of chloroquine intake. The concentrations of chloroquine in plasma and whole blood were measured by high-performance liquid chromatography for 192 h. 3. Activated charcoal reduced the areas under the plasma and whole blood chloroquine concentration-time curves (AUC) from 0 to 192 h, the total AUCs, and the peak concentrations by 99% (P less than 0.001). 4. Chloroquine was very effectively bound by activated charcoal in vitro, even at low charcoal-chloroquine ratios. For example, at a ratio of 5:1, about 98% of chloroquine was bound. 5. Activated charcoal should be very effective in reducing the absorption of that fraction of chloroquine dose which is in the stomach at the time of charcoal administration. Because the acute toxicity of chloroquine is extremely high and death usually occurs within 1-3 h of overdosage, charcoal should be given as early as possible in suspected chloroquine intoxication.     

Prevention of amlodipine absorption by activated charcoal: effect of delay in charcoal administration

Aims The purpose of this study was to investigate the effect of activated charcoal on the absorption of amlodipine, with special reference to delayed charcoal administration.
Methods Thirty-two healthy volunteers, eight subjects in four parallel groups, ingested 10 mg of amlodipine on an empty stomach. Activated charcoal (25 g in 300 ml of water) was ingested either immediately afterwards or 2 h or 6 h after amlodipine, or amlodipine was ingested with 300 ml of water only (control). Plasma concentrations and the cumulative excretion of amlodipine into urine were measured by GC-MS for 96 h and 72 h, respectively. In addition, adsorption of amlodipine to charcoal was studied in vitro .
Results Activated charcoal administered immediately after amlodipine reduced the amlodipine AUC(0,96 h) and the 72-h urinary excretion by 99% ( P <0.0005). After a delay of 2 h in charcoal administration the AUC(0,96 h) was reduced by 49% ( P =0.001), but after a delay of 6 h the reduction was 15% only ( P =NS). At a charcoal: drug ratio of 5:1, about 90% of amlodipine was adsorbed by charcoal in vitro; at ratios of 10:1 and 20:1, adsorption was practically complete.
Conclusions Activated charcoal almost completely prevented amlodipine absorption when administered immediately after amlodipine ingestion. Charcoal also markedly reduced amlodipine absorption when given 2 h after amlodipine; in amlodipine overdose, administration of charcoal may be beneficial even later. We conclude that administration of activated charcoal is the method choice to prevent absorption of amlodipine in amlodipine overdose.     

Effect of magnesium citrate on the adsorptive capacity of activated charcoal for sodium salicylate

The effects of an added saline cathartic (magnesium citrate) on the in vitro adsorption of sodium salicylate by activated charcoal were determined at different pH levels. At low pH added magnesium citrate reduced salicylate adsorption. However, at high pH added magnesium citrate enhanced adsorption. These results indicate that magnesium citrate should have no detrimental effect on the action of activated charcoal in vivo. Indeed, a slight beneficial effect is suggested by this and other studies.     

In vitro adsorption of tilidine HCl by activated charcoal

In vitro studies were carried out in order to determine the adsorption of tilidine HCl, a narcotic analgesic, by activated charcoal (max. adsorption capacity 185.5 mg/g of charcoal). The path of the adsorption isotherms at pH 1.2 and 7.5 suggests that the in vivo adsorption of tilidine HCl may be increased when the drug passes from the stomach to the intestine, unless the intestinal content exerts a displacing effect. Nevertheless, the adsorption was dependent on the quantity of activated charcoal used, becoming more complete when the quantity of activated charcoal was increased. The effects of additives on the adsorption capacity of activated charcoal were also investigated in vitro. Ethanol, sorbitol and sucrose significantly reduced drug adsorption, while cacao powder, milk and starch had no effect on tilidine adsorption. At an acid pH, Federa Activated Charcoal significantly adsorbed more drug than either Norit A or Activated Charcoal Merck.     

A ready-to-use activated charcoal mixture

A practical, ready-to-use preparation of activated charcoal (AZU mixture) for application in toxicology has been formulated. Tb establish its efficacy, the formulation was testedin vitro and in dogs. Thein vitro adsorption capacity was compared to that of freshly prepared charcoal suspension in water (CW) and to Carbomix^®. Langmuir adsorption coefficients demonstrated small but clinically insignificant differences in adsorption capacity between the preparations. The laxative sodium sulfate did not reduce the adsorption capacity of charcoalin vitro. Dogs were given 60 mg of paracetamol per kg as an oral solution followed by 5 g of activated charcoal preparation. The area under the plasma concentration versus time curve (control 2955±353 mg·min^–1·1^–1) was significantly reduced following CW (921±453) and AZU (786±270). The premixed AZU charcoal formulation is efficacious, inexpensive and overcomes the problems of bed-side preparation. An isolated vascularly perfused rat small intestine can be used to describe the effect of activated charcoal on the intestinal secretion of theophylline.     

Heparin adsorption on activated charcoal

By vitro studies have shown that sodium heparin adsorbs significantly at pH 7.4 conditions onto a typical activated charcoal. These results imply that enhanced heparin removal from blood should be anticipated in hemoperfusion systems that utilize uncoated charcoals.     

Hydrated sodium calcium aluminosilicate (HSCAS), acidic HSCAS,and activated charcoal reduce urinary excretion of aflatoxin M1 in turkey poults. Lack of effect by activated charcoal on aflatoxicosis

In one experiment, the effect of inorganic sorbents on the metabolic fate of aflatoxin B₁ (AFB₁) was studied in turkey poults. At 5 weeks of age, female poults were surgically colostomized and 9 days later orally dosed with 0.75 mg AFB₁/kg BW. Hydrated sodium calcium aluminosilicate (HSCAS), acidic HSCAS, and activated charcoal (AC) were tested, by concomitant administration with AFB₁. Urine was collected up to 48 h post-dosing and analyzed for aflatoxin M₁ (AFM₁) which was the major metabolite found in all treatment groups. Hydrated sodium calcium aluminosilicate, previously proven beneficial in alleviating aflatoxicosis in farm animals, reduced urinary AFM₁ output when orally dosed simultaneous with AFB₁. Also, acidic HSCAS and AC significantly decreased AFM₁ excretion when administered concomitantly with AFB₁. A second experiment was conducted to evaluate the ability of two types of AC to modify aflatoxicosis when added to aflatoxin (AF)-contaminated (from culture material) diets of turkey poults. Although AC was able to decrease AFM₁ excretion in the first experiment, no protective effects from AF toxicity were observed in the feeding study.     

The effect of repeated-dose activated charcoal on the Pharmacokinetics of sodium valproate in healthy volunteers

Aims We investigated the effects of repeated-dose charcoal administered several hours after sodium valproate on the pharmacokinetics of a single dose of the drug in healthy volunteers.
Methods The pharmacokinetics of sodium valproate were studied in seven healthy volunteers after administration of a syrup (300 mg) on two occasions, one of which was followed by administration of repeated doses of oral charcoal starting 4 h after the drug up to 32 h (total dose 80 g).
Results Valproate was rapidly absorbed with maximum concentrations 1 h after administration. The area under the plasma concentration-time curve to 48 h (AUC (0,48 h)) was 408 ± 114.5 (s.d.)mgl⁻¹ h in the control phase and 398 ± 108.6 mgl⁻¹ h after charcoal and the t _1/2 elimination was 20 ± 6.8 h in the control phase, and 22 ± 9.2 h after charcoal (NS).
Conclusions Repeated-dose activated charcoal does not appear to enhance the rate of elimination of sodium valproate after therapeutic doses of the drug and any beneficial effect of charcoal in overdose may be to prevent absorption of valproate still present in the gut.