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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).

The effect of added food mixture (as if food was present in the stomach of an intoxicated patient) or 4 different types of ice cream (added as a flavouring and lubricating agent) on the adsorption of paracetamol (acetaminophen) to 2 formulations of activated charcoal was determined in vitro and compared with results from previous investigations showing a maximum adsorption capacity to the two activated charcoal-water slurries at about 0.62-0.72 g paracetamol/g activated charcoal. Activated charcoal (Carbomix or Norit Ready-To-Use), simulated gastric (pH 1.2) or intestinal (pH 7.2) fluid, and paracetamol were mixed with either food mixture or ice cream followed by one hr incubation. The maximum adsorption capacity of paracetamol to activated charcoal was calculated using Langmuirs adsorption isotherm. Paracetamol concentration was analyzed using high pressure liquid chromatography. In the presence of food, the paracetamol adsorption capacity of the 2 activated charcoals was reduced by max. 19% (P<0.05) for Carbomix(R) and by max. 11% (P<0.05) for Norit Ready-to-use compared to control without food (Hoegberg et al. 2002). Depending on which type of ice cream was mixed with the charcoal, the reductions compared to control (Hoegberg et al. 2002) varied between 11% and 26%. Even though a reduction in drug adsorption to activated charcoal was observed when food mixture or ice cream was added, the remaining adsorption capacity of both types of activated charcoal theoretically was still able to provide an effective gastrointestinal decontamination.

Aims: Activated charcoal is now being recommended for patients who have ingested potentially toxic amounts of a poison, where the ingested substance adsorbs to charcoal. Combination therapy with gastric lavage and activated charcoal is widely used, although clinical studies to date have not provided evidence of additional efficacy compared with the use of activated charcoal alone. There are also doubts regarding the efficacy of activated charcoal, when administered more than 1 h after the overdose. The aim of this study was to examine if there was a difference in the effect of the two interventions 1 h post ingestion, and to determine if activated charcoal was effective in reducing the systemic absorption of a drug, when administered 2 h post ingestion., Methods: We performed a four-limbed randomized cross-over study in 12 volunteers, who 1 h after a standard meal ingested paracetamol 50 mg kg(-1) in 125 mg tablets to mimic real-life, where several factors, such as food, interfere with gastric emptying and thus treatment. The interventions were activated charcoal after 1 h, combination therapy of gastric lavage followed by activated charcoal after 1 h, or activated charcoal after 2 h. Serum paracetamol concentrations were determined by h.p.l.c. Percentage reductions in the area under the curve (AUC) were used to estimate the efficacy of each intervention (paired observations)., Results: There was a significant (P<0.005) reduction in the paracetamol AUC with activated charcoal at 1 h (median reduction 66%, 95% confidence intervals 49, 76) compared with controls, and a significant (P<0.01) reduction for gastric lavage followed by activated charcoal at 1 h (median reduction 48.2%, 95% confidence interval 32.4, 63.7) compared with controls. There was no significant difference between the two interventions (95% confidence interval for the difference -3.8, 34.0). Furthermore, we found a significant (P<0.01) reduction in the paracetamol AUC when activated charcoal was administered 2 h after tablet ingestion when compared with controls (median 22.7%, 95% confidence intervals 13.6--34.4)., Conclusions: These results suggest that combination treatment may be no better than activated charcoal alone in patients presenting early after large overdoses. The effect of activated charcoal given 2 h post ingestion is substantially less than at 1 h, emphasizing the importance of early intervention.

Background: Paracetamol (acetaminophen) intoxication often in combination with ethanol, is seen commonly in overdose cases. Doses of several grams might be close to the maximum adsorption capacity of the standard treatment dose (50g) of activated charcoal. The aim of this study was to determine the maximum adsorption capacity for paracetamol for two types of high surface-activated charcoal [Carbomix and Norit Ready-To-Use (not yet registered trademark in Denmark) both from Norit Cosmara, Amersfoort, The Netherlands] in simulated in vivo environments: At pH 1.2 (gastric environment), at pH 7.2 (intestinal environment), and with and without 10% ethanol., Methods: Activated charcoal, at both gastric or intestinal pHs, and paracetamol were mixed, resulting in activated charcoal-paracetamol ratios from 10:] to 1:1. In trials with ethanol, some of the gastric or intestinal fluid was replaced with an equivalent volume of ethanol, resulting in an ethanol concentration of 10% v/v. After incubation, the concentration of unabsorbed paracetamol was analyzed by high-performance liquid chromatography. The maximum adsorption capacity of paracetamol to activated charcoal was calculated as mg paracetamol adsorbed/g activated charcoal, using Langmuir's isotherm., Results: Carbomix [95% confidence limits are shown in square brackets]: 623.7 [612.8;634.5] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 626.2 [611.6;640.9] mg paracetamol adsorbed/g activated charcoal (pH 7.2); Norit Ready-To-Use: 693.6 [676.8;710.5] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 722.6 [687.4;757.9] mg paracetamol adsorbed/g activated charcoal (pH 7.2). For experiments with ethanol (10% v/v) the results with Carbomix were 465.7 [449.2;482.2] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 498.6 [481.8;515.6] mg paracetamol adsorbed/g activated charcoal (pH 7.2); with Norit Ready-To-Use: 617.2 [606.6;627.7] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 640.6 [624.9;656.4] mg paracetamol adsorbed/g activated charcoal (pH 7.2)., Conclusion: Under conditions simulating immediate treatment with charcoal, a standard dose of 50 g of either of the two tested activated charcoals adsorbed a sufficient amount of paracetamol to be beneficial in the treatment of the majority of overdoses of this drug. For both types of activated charcoal, with or without ethanol, there was no significant difference in the adsorption of paracetamol at pH 1.2 and 7.2. Norit Ready-To-Use had a larger maximum adsorption capacity than Carbomix, and was not as sensitive as Carbomix to environmental changes (pH and ethanol). The presence of 10% ethanol lowered the adsorption capacity of the two tested activated charcoal preparations by an amount that might be clinically relevant in cases of intoxications by high-gram doses.

Clinical pharmacology was established quite recently in Denmark as a medical specialty. It comprises--among other items--clinical pharmacological drug information service, the primary aim of which is to provide service to health personnel with clinical responsibility involving drugs and specific patient-related questions. Questions forwarded to the clinical pharmacological drug information service at two Copenhagen hospitals have been summarized. The questions were categorized according to the profession and the affiliation to the health care system of the inquirer as well as the nature of the question. At the two hospitals, 118 and 77 questions were answered from January 1st 1997 to June 1st 1998, respectively. Physicians employed at hospitals were responsible for the majority of the questions. Most questions concerned adverse drug reactions, choice of therapy/drug, and therapy during pregnancy or breast feeding.

This study was performed to investigate the possible differences between prescribed medicine, as entered in the hospital record, and the medicine dispensed to the patients according to the nurse's dispensing records (NDR's) in two clinical departments at a Copenhagen University Hospital. Discrepancies were defined as either dosage differences or drugs only present in one file, and were divided into major and minor discrepancies, according to clinical significance. In the first department, discrepancies were found in 61.4% of the records, and major discrepancies were found in 35.1%. In the second department, discrepancies were found in 70.5% of the cases, and major discrepancies in 42.5%. No correlation was found between the number of drugs per patient and the number of discrepancies. A significant difference exists between what is prescribed, and what is dispensed. This can have clinical as well as legal consequences.