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Comparison of the adsorption capacities of an activated-charcoal--yogurt mixture versus activated-charcoal--water slurry in vivo and in vitro.

BACKGROUND: An activated charcoal--yogurt mixture was evaluated in vivo to determine the effect on the gastrointestinal absorption of paracetamol, as compared to activated-charcoal--water slurry. The potential advantage of the activated-charcoal--yogurt mixture is a better palatability and general acceptance by the patients without loss of efficacy. In addition, paracetamol adsorption studies were carried out in vitro to calculate the maximum adsorption capacity of paracetamol to activated-charcoal--yogurt mixture. METHODS: In vivo: A randomized crossover study on 15 adult volunteers, using paracetamol 50 mg/kg as a simulated overdose. Each study day volunteers were given a standard meal 1 h before paracetamol, then 50 g activated charcoal 1 h later in either of two preparations: standard water slurry or mixed with 400 mL yogurt. Paracetamol serum concentrations were measured using HPLC. The areas under the concentration-time curve (AUC) of the two preparations were compared and used to estimate the efficacy of each preparation. The palatability of both preparations was evaluated using a visual-analogue scale where the volunteers were asked to evaluate the appearance, smell, flavor, texture, ability to swallow, and overall impression of the mixtures. The time spent to consume the activated charcoal was also registered. In vitro: Activated charcoal, simulated gastric (pH 1.2) or intestinal (pH 7.2) fluid, and paracetamol were mixed with yogurt followed by 1 h incubation. The maximum adsorption capacity of paracetamol to activated charcoal was calculated using Langmuir's adsorption isotherm. Paracetamol concentration was analyzed using HPLC. RESULTS: In vivo there was no significant difference (p > 0.05) in the AUC of paracetamol between the two activated-charcoal preparations. Geometric mean values and 95% CI for the AUCs were (in mg/l x min): 6307 (4932-8065) for the activated charcoal--water slurry and 6525 (5111-8330) for the activated charcoal--yogurt mixture. The palatability study showed significant difference (p < 0.05) only in duration of administration, in favor of the activated charcoal--water slurry. In vitro the maximum adsorption capacity of activated charcoal with added yogurt was 544 mg paracetamol/g activated charcoal (pH 1.2), and 569 mg paracetamol/g activated charcoal (pH 7.2). CONCLUSION: The two activated-charcoal preparations showed equal (NS) absorption reduction of paracetamol in vivo. Mixing activated charcoal with yogurt rather than water prolonged the ingestion time, but did not improve the palatability in adults. The presence of yogurt reduced the adsorption capacity in vitro by 9-13% (p < 0.05) compared to control without yogurt (previous study with the same setup).

Acetaminophen↗

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 of choice to prevent absorption of amlodipine in amlodipine overdose.

Adsorption↗

Comparison of a charcoal sorbent fiber with commercial charcoals for hemoperfusion.

A charcoal sorbent fiber (Enka, F.R.G.), was assessed for impurities, surface area, and adsorptive properties of its native charcoal, and compared with other uncoated activated charcoals. In vivo and in vitro hemocompatibility of the fiber were assessed as well as the adsorptive properties for endogenous toxins. The charcoal of the fiber had few impurities and a high surface area of 1,200 m2/g charcoal. For measuring the adsorptive speeds, 2 g of the uncoated charcoals were milled and screened to a particle size of 150-250 microns (Enka; 30-40 microns) and then mixed with the solutions of the individual solutes. The charcoal types of Enka, used in the charcoal sorbent fiber, and of Sutcliffe Speakman, used in the acrylic hydrogel coated charcoal, exhibited the highest adsorptive rates for bromthalein (middle molecular weight marker) and inulin (high molecular weight marker). No hematological differences among the various charcoals were found during the in vivo hemoperfusions. In the in vitro hemoperfusions with heparinized fresh blood, the fibers showed the lowest loss of leucocytes and thrombocytes. In the in vitro evaluation of the absorbents for hepatic support, the charcoal fiber and the petroleum pitch charcoal of Asahi had the best adsorptive properties for substances in the low molecular weight range.

Adsorption↗

Effect of charcoal and sorbitol-charcoal suspension on the elimination of intravenous phenobarbital.

The effects of two different oral charcoal suspensions on the elimination of a 200 mg/70 kg, 1 h intravenous (i.v.) infusion of phenobarbital and the tolerances of the two regimens were determined in a randomized crossover study in six healthy male volunteers. Phenobarbital was given i.v. alone or together with 105 g of oral activated charcoal suspension or with 105 g of a commercially available sorbitol-charcoal suspension over a 36-h period. A 13-34% decrease in the area under the serum concentration time curve (AUC) for 0-60 h occurred with the administration of the activated charcoal, and a 19-52% decrease occurred with the commercial sorbitol-charcoal regimen. The mean apparent systemic clearance of total phenobarbital increased from 0.089 +/- 0.019 ml/min/kg to 0.141 +/- 0.029 and 0.146 +/- 0.036 ml/min/kg with the charcoal and sorbitol-charcoal treatments, respectively. No significant change in the fraction of phenobarbital bound to protein was detected. The charcoal regimen caused constipation in one subject. All subjects taking the sorbitol-charcoal preparation experienced diarrhea; there were no changes in electrolytes with either charcoal suspension. All subjects preferred the sorbitol-charcoal preparation.

Adult↗

Effect of activated charcoal on the pharmacokinetics of pholcodine, with special reference to delayed charcoal ingestion.

We conducted a randomized study with four parallel groups to investigate the effect of single and multiple doses of activated charcoal on the absorption and elimination of pholcodine administered in a cough syrup. The first group received 100 mg of pholcodine on an empty stomach with water only (control); the second group took 25 g of activated charcoal immediately after pholcodine; the third group received 25 g of activated charcoal 2 h and the fourth group 5 h after ingestion of the 100-mg dose of pholcodine. In addition, the fourth group received multiple doses (10 g each) of charcoal every 12 h for 84 h. Blood samples were collected for 96 h and urine for 72 h. Pholcodine concentrations were measured by high-performance liquid chromatography. A significant reduction in absorption was found when charcoal was administered immediately after pholcodine; the AUC0-96h was reduced by 91% (p < 0.0005), the Cmax by 77% (p < 0.0005), and the amount of pholcodine excreted into urine by 85% (p < 0.0005). When charcoal was administered 2 h after pholcodine, the AUC0-96h was reduced by 26% (p = 0.002), the Cmax by 23% (p = NS), and the urinary excretion by 28% (p = 0.004). When administered 5 h after pholcodine, charcoal produced only a 17% reduction in the AUC0-96h (p = 0.06), but reduced the further absorption of pholcodine still present in the gastrointestinal tract at the time of charcoal administration, as measured by AUC5-96h (p = 0.006). Repeated administration of charcoal failed to accelerate the elimination of pholcodine. We conclude that activated charcoal is effective in preventing the absorption of pholcodine, and its administration can be beneficial even several hours after pholcodine ingestion.

Adult↗

Effect of charcoal-drug ratio on antidotal efficacy of oral activated charcoal in man.

The effect of charcoal-drug ratio on the antidotal efficacy of oral activated charcoal was studied in six healthy volunteers in a randomized cross-over study and compared with the adsorption capacity of activated charcoal in vitro. Aminosalicylic acid (PAS) 1 g and 5 g were ingested on an empty stomach in 30 ml of water. Immediately afterwards the subjects ingested 50 g of activated charcoal in 300 ml of water or 300 ml of water only. PAS 10 g 20 g were only given with 50 g of activated charcoal administered immediately afterwards. The plasma concentrations and the cumulative excretion of PAS into urine were measured for 48 h. Increasing the dose of PAS from 1 g to 20 g reduced the antidotal efficacy of activated charcoal: at a charcoal-drug ratio of 50:1 under 5% of the dose was absorbed but at a ratio of 2.5:1 about 37%. These data correlated well to the saturation of adsorption capacity of charcoal in vitro. To minimize the possibility of saturation of the adsorption capacity of charcoal in acute intoxications where the amount and type of drug taken is usually unknown, large doses (50-100 g) of activated charcoal should be used.

Administration, Oral↗

The effect of activated charcoal on the absorption of fluoxetine, with special reference to delayed charcoal administration.

The effect of activated charcoal on fluoxetine (40 mg) absorption, with special reference to delayed charcoal administration, was investigated in a randomized study with four parallel groups of eight Healthy volunteers. The first group ingested fluoxetine on an empty stomach with water only (control). The second group received 25 g of activated charcoal as a suspension immediately after fluoxetine. The third and fourth groups took fluoxetine with water and received 25 g of charcoal 2 or 4 hr after fluoxetine. Timed blood samples were taken and plasma fluoxetine and norfluoxetine concentrations were measured by GC for 96 hr. When charcoal was administered immediately after fluoxetine, the AUC (0-96 hr) of fluoxetine was reduced by more than 96% (P < 0.0005) and the Cmax by more than 98% (P < 0.0005). The reduction in the AUC (0-96 hr) and Cmax of norfluoxetine was similar to that of fluoxetine. When the administration of charcoal was delayed 2 or 4 hr, there was a non-significant mean reduction of 16% and 23% in the AUC (0-96 hr) of fluoxetine. Similarly, the Cmax was not significantly reduced by charcoal given 2 or 4 hr later. Also, the half-life of fluoxetine was not significantly reduced (by 25%) by the late administration of charcoal. We conclude that activated charcoal, ingested immediately after fluoxetine, practically completely prevents the gastrointestinal absorption of fluoxetine. However, regardless of the relatively slow absorption of fluoxetine, delaying charcoal administration 2-4 hr greatly reduces its antidotal efficacy.

Adult↗

Superiority of activated charcoal alone compared with ipecac and activated charcoal in the treatment of acute toxic ingestions.

A prospective, randomized clinical trial compared the clinical effectiveness of syrup of ipecac and activated charcoal to that of activated charcoal alone in the treatment of acute toxic ingestions. Two hundred adult patients with mild to moderate oral overdoses were entered into the trial. Patients receiving only activated charcoal were discharged from the emergency department in significantly (P less than or equal to .05) less time than those receiving both syrup of ipecac and activated charcoal (6.0 +/- 0.3 vs 6.8 +/- 0.2 hours, respectively). The percentage of patients requiring nonpsychiatric hospitalizations was not significantly different between the two groups (11.2% vs 14.0%, respectively). For the hospitalized patients, the length of time spent in the ICU and in the hospital was not statistically different between the two groups. A complication rate of 5.4% was found with the ipecac and activated charcoal treatment compared with a 0.9% complication rate in the activated charcoal group (P less than or equal to .05). Three episodes of aspiration pneumonitis occurred after administration of ipecac and activated charcoal, while no episodes of aspiration were noted after treatment with only activated charcoal. Together, these data are consistent with the recommendation that ED treatment with activated charcoal alone be the gastrointestinal decontamination procedure of choice for the routine mildly-to-moderately orally poisoned adult patient.

Adult↗

Activated charcoal is more effective than equilibrium dialysis in removing Chinese medicines Chan Su and Dan Shen from serum and activated charcoal also prevents further absorption of these agents from G.I. tract in mice: monitoring the effect in clinical laboratory by measuring digoxin activity in serum.

BACKGROUND: Chinese medicines are freely available without prescription and are widely used by the general population. Chan Su and Dan Shen are both indicated for the treatment of cardiac diseases. Severe toxicity from Chan Su has been reported. We studied the possibility of removing Chan Su and Dan Shen from human sera using activated charcoal and equilibrium dialysis, and also examined the potential benefit of preventing absorption of these agents from the G.I. tract in the mouse model. METHODS: For in vitro studies, drug-free serum pools were supplemented with Chan Su or Dan Shen and then either treated with activated charcoal (10 and 25 mg/ml), or passed through a column packed with activated charcoal. Serum pools supplemented with Chan Su or Dan Shen were also subjected to equilibrium dialysis against phosphate buffer (pH 7.4) using dialysis membrane with molecular cut-off of 25,000 Da. Removal of Chan Su or Dan Shen from the serum was monitored by measuring the apparent digoxin concentration using the fluorescence polarization immunoassay (FPIA) for digoxin (Abbott Laboratories). RESULTS: We observed the fast and effective removal of both Chan Su and Dan Shen from the serum by activated charcoal. We also observed significant removal of both Chan Su and Dan Shen when the serum pools containing these Chinese medicines were passed through columns packed with activated charcoal. Although equilibrium dialysis was also effective in removing these Chinese medicines from the serum, 24 h was required for complete removal of Dan Shen activity, and for Chan Su, complete removal was not achieved even after 24 h. In our in vivo model, we observed significantly less digoxin activity in the group of mice that received activated charcoal compared to the control group. CONCLUSIONS: Activated charcoal is effective in preventing absorption of these Chinese medicines from the G.I. tract and can also remove these agents from the serum.

Animals↗

Thermodynamic evaluation of activated charcoal as a poison antidote by high-performance liquid chromatography. II: In vitro method for the evaluation of activated charcoal as a poison antidote.

A previous report detailed the derivation and validation of an equation for calculating the Gibbs free energy of liquid-solid adsorption via high-performance liquid chromatography (HPLC). This study utilizes an improved form of that equation in conjunction with an in vitro model of solute adsorption to give an ordered listing of the antidotal activity of activated charcoal towards different drugs and other chemicals. The in vitro model consists of an activated charcoal column with a nominal particle diameter of 15 micron and a surface area of 447 x 10(4) cm2/g, together with a series of acetonitrile:water mobile phases at pH 3. A simple and efficient procedure was developed for ranking the solutes. First, each compound was run in an acetonitrile(ACN):water mobile phase chosen to give a convenient retention time and ideal chromatographic response. The capacity factor for this mobile phase was extrapolated to give a predicted capacity factor for a 35:65 (v/v) ACN:water mobile phase using an empirical equation developed from the exhaustive chromatography of four standard compounds (phenobarbital, strychnine, cyclohexanone, methyl ethyl ketone) in a variety of ACN:water mobile phases. In addition to the standards, 12 other compounds (glutethimide, chlordiazepoxide, quinine, brucine, d-propoxyphene, pentobarbital, methyprylon, methadone, meperidine, codeine, antipyrine, morphine) were evaluated. Based on these data, the Gibbs free energies of liquid-solid adsorption for these compounds were calculated and used to evaluate activated charcoal as a poison antidote for them. The results indicate that a rapid and accurate estimation of the utility of activated charcoal as an antidote for drugs and toxic substances can be obtained from a single chromatographic run of the test compound.

Adsorption↗

Assessment of the elution of charcoal, cellulose acetate, and other particles from cigarettes with charcoal and activated charcoal/resin filters.

This experiment was designed to study the release of cellulose acetate fibers, charcoal, and other particles from cigarettes with charcoal and activated charcoal/resin filters. For the first time in such studies, efforts were made to identify the particles that were eluted using other analytical techniques in addition to light microscopy. Other corrective measures were also implemented. During the studies it was found that trimming of larger filters to fit smaller filter housings introduced cellulose acetate-like particles from the fibers of the filter material. Special, custom made-to-fit filters were used instead. Tools such as forceps that were used to retrieve filters from their housings were also found to introduce fragments onto the filters. It is believed that introduction of such debris may have accounted for the very large number of cellulose acetate and charcoal particles that had been reported in the literature. Use of computerized particle-counting microscopes appeared to result in excessive number of particles. This could be because the filter or smoke pads used for such work do not have the flat and level surfaces ideal for computerized particle-counting microscopes. At the high magnifications that the pads were viewed for particles, constant focusing of the microscope would be essential. It was also found that determination of total particles by using extrapolation of particle count by grid population usually gave extremely high particle counts compared to the actual number of particles present. This could be because particle distributions during smoking are not uniform. Lastly, a less complex estimation of the thickness of the particles was adopted. This and the use of a simple mathematical conversion coupled with the Cox equation were utilized to assess the aerodynamic diameters of the particles. Our findings showed that compared to numbers quoted in the literature, only a small amount of charcoal, cellulose acetate shards, and other particles are released. It was also shown that those particles would have a low likelihood of reaching the lung.

Adhesives↗

"Superactive" charcoal adsorbs drugs as fast as standard antidotal charcoal.

Experimental data on the uptake of two test drugs by powdered Amoco PX-21 and Norit A activated charcoals in stirred-batch tests indicate that the rate of uptake by the Amoco charcoal is equal to, or higher than, the uptake rate by Norit A. In contrast to the conjecture of Medema [1], the superactive Amoco charcoal is not kinetically inferior to Norit A. The superactive charcoal remains highly recommended for antidotal uses.

Absorption↗

In-vivo comparison of the adsorption capacity of "superactive charcoal" and fructose with activated charcoal and fructose.

This study was undertaken to assess the in-vivo capacity of two activated charcoal products to adsorb aspirin after its ingestion by seven healthy volunteers. The two products, Norit-A and Super-Sorb, were combined with fructose solution and administered after the subjects ingested 975 mg of aspirin. Urinary excretion of salicylates was measured during both charcoal administration phases and after ingestion of aspirin alone in all subjects. Results showed statistically significant differences in salicylate excretion between all phases. Super-Sorb ("superactive charcoal") adsorbed almost twice (1.7) as much as aspirin as the regular activated charcoal, Norit-A. Super-Sorb therefore has a greater in-vivo adsorption capacity for aspirin and should be a more effective antidote in poisonings with this drug.

Adjuvants, Pharmaceutic↗

Toxicant adsorption on activated charcoal: is the fraction adsorbed a unique function of the charcoal:adsorbate ratio?

In several recent studies the adsorption of toxicants on activated charcoal has been reported graphically in the form of plots presenting the fraction of toxicant unadsorbed at equilibrium (F) as a unique function of the ratio (R) of the amount of activated charcoal to that of total toxicant. Derivation of the mathematical relationship between these two variables from either the Freundlich or Langmuir isotherms reveals F is not uniquely defined by R, unless the amount of activated charcoal, the equilibrium concentration of the toxicant, or its initial concentration is kept constant. For two agents known to adhere to the Freundlich isotherm, paraldehyde and metaldehyde, a good agreement was obtained between the F and R values predicted by the derived equations and those observed experimentally. The usefulness of F versus R plots is discussed.

Adsorption↗

Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal.

Activated charcoal usually provides effective and safe treatment for drug overdose. We describe a patient who developed bronchiolitis obliterans and respiratory failure following aspiration of activated charcoal. This patient had a markedly reduced vital capacity with roentgenographic evidence of airtrapping. Chest roentgenograms did not demonstrate the large amount of charcoal identified at postmortem examination.

Adolescent↗

Coating charcoal with polyacrylate-polymethacrylate copolymer for haemoperfusion. III: The effect of the coat thickness on the adsorptioncapacity of the coated charcoal and its adsorptivity to small and middle size molecules.

In this study, the effect of the coat thickness of polyacrylate-polymethacrylate copolymer on the adsorption capacity of activated charcoal to methylene blue as a model marker was investigated by constructing both Langmuir and Freundlich isotherms. It was found that the coat thickness significantly affected the adsorption coefficient of the coated charcoal to methylene blue as is reflected by the attractive forces between the adsorbent and the adsorbate. This effect is understandable as the membrane will act as a barrier between the adsorbent and the adsorbate. The coat thickness also had some effect on the adsorption capacity of activated charcoal but not as much as it affected the adsorption coefficient. The data followed the Freundlich isotherm more closely than the Langmuir equation. The effect of the coat thickness on the adsorption of selected drugs of different molecular size was also investigated using theophylline, paracetamol, sodium phenobarbital, creatinine and vitamin B12 as model drugs. The results showed that the adsorption patterns of theophylline, paracetamol and sodium phenobarbital were more or less similar. The apparent coating thickness did not affect the extent of adsorption of these model drugs and there was little effect on the adsorption rate especially during the first 15 min. The adsorption of vitamin B12 and creatinine showed completely different patterns which are discussed in detail.

Acrylic Resins↗

In vitro drug adsorption to charcoal, silicas, acrylate copolymer and silicone oil with charcoal and with acrylate copolymer.

1. The relative binding constants of four drugs to charcoal, silicone oil silicas and acrylate copolymers was studied using an in-vitro binding technique. 2. The maximum adsorption capacity (K2) was chosen as a measure of the degree of binding and calculated by fitting to the Langmuir equation. 3. Charcoal alone was shown to be the most effective of the adsorbents chosen. The possible use of silicone oils as an adsorbent delivery vehicle in treatment of overdose is discussed.

Acetaminophen↗

A new combined enzyme-charcoal system adsorption on charcoal followed by polymer coating.

A method is described for a new combined enzyme-charcoal system. A model enzyme, urease, was adsorbed on activated charcoal granules which was then coated with ultrathin cellulose nitrate. The assayed activity of this immobilized enzyme was 28.1% /+- 3.12% (mean /+- S.D.) of the activity of urease in solution. The enzyme did not leak out after immobilization and worked efficiently. The assayed urease activity increased with greater amounts of urease/gm immobilized enzyme, but reached a plateau after 40 sumner units/gm. Immobilized urease has good storage and operational stabilities at refrigerator, room and body temperatures. In-vivo studies show that about 90% conversion urea in one single pass is possible.

Adsorption↗