Helle R. Angelo

Intravenous lidocaine infusion — a new treatment of chronic painful diabetic neuropathy?

In a randomized double-blind, cross-over study the effect of intravenous lidocaine (5 mg/kg body weight) on the symptoms and signs of painful diabetic neuropathy of more than 6 months duration has been evaluated. Using a clinical symptom scale, there was significant beneficial effect 1 and 8 days after lidocaine infusion compared to after saline infusion (P less than 0.05 and P less than 0.02, respectively). The duration of the individual effect ranged from 3 to 21 days. Lidocaine infusion had no effect on the objective measurements of neuropathy. Intravenous lidocaine infusion seems to be a new alternative treatment of chronic painful diabetic neuropathy.

Stereoselective pharmacokinetics of methadone in chronic pain patients.

SummaryTen patients with chronic pain were randomized to an open, balanced, crossover study. Each patient received two different preparations of racemic methadone, i.e., tablets and intravenous infusion. The pharmacokinetic parameters of the R- and S-enantiomers of the racemate are reported. The ana

Enantioselective high-performance liquid chromatographic method for the determination of methadone in serum using an AGP and a CN column as chiral and analytical column, respectively

A simple and sensitive HPLC method with ultraviolet absorption detection at 200 nm is described for the determination of methadone enantiomers in human serum, using dextropropoxyphene as an internal standard and organic solvent extraction. Separation was performed on two serially coupled columns, CN and Chiral AGP, with a mobile phase consisting of acetonitrile, dimethylocytlamine and phosphate buffer. Using 1.0 ml of serum, 5 nmol/1 of each enantiomer could be determined with an acceptable precision. No interactions from several drugs were observed. The method has been successfully used in a pharmacokinetic study. More than 2500 serum samples have been separated on the same AGP column with acceptable selectivity and resolution.

Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti‐epileptic drugs in man

Interactions between analgesics and anti‐epileptic drugs may sometimes present a serious clinical problem. The aim of the study was to investigate the influence of usually applied doses of dextropropoxyphene (DPX) on the steady state levels of carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB).

Enantioselective high-performance liquid chromatographic method for the determination of methadone and its main metabolite in urine using an AGP and a C8 column coupled serially

A simple and sensitive method for the enantioselective high-performance liquid chromatographic determination of methadone and its main metabolite, EDDP, in human urine is described. (-)-(R)-Methadone, (+)-(S)-methadone, (+)-(R)-EDDP, (-)-(S)-EDDP and imipramine as an internal standard are detected by ultraviolet detection at 200 nm. The enantiomers of methadone and EDDP were extracted from human urine by a simple liquid-liquid extraction procedure. The extracted sample was reconstructed in mobile phase and the enantiomers of methadone and EDDP were quantitatively separated by HPLC on a short analytical LiChrospher RP8 column coupled in series with a chiral AGP column. Determination of all four enantiomers was possible in the range of 0.03 to 2.5 microM. The recoveries of methadone enantiomers and EDDP enantiomers added to human urine were about 90% and 80%, respectively. The method was applicable for determination of methadone enantiomers and the enantiomers of its main metabolite in urine samples from methadone maintenance patients and patients suffering from severe chronic pain.

Lidocaine treatment of painful diabetic neuropathy and endogenous opioid peptides in plasma

Intravenous infusion of lidocaine has a pain-relieving effect in patients with painful diabetic neuropathy. We measured plasma beta-endorphin (beta-EP), dynorphin immunoreactivity (DYN), and met-enkephalin (MET) before and after lidocaine infusion in 8 patients with painful diabetic neuropathy and in 10 controls. The pretreatment level of beta-EP and DYN was identical in the two groups. After lidocaine, beta-EP increased in diabetic patients from 3.4 to 5.5 pmol/L (median) (p less than 0.02) and in controls from 3.4 to 5.0 pmol/L (p less than 0.02). The concentration of DYN was stable, and MET was undetectable before and after lidocaine. Lidocaine reduced symptoms and pain score in diabetic patients was uncorrelated with the changes in beta-EP. Intravenous lidocaine increased plasma beta-EP and diminished complaints in patients with painful diabetic neuropathy.

Determination of acetaldehyde in human blood by a gas chromatographie method with negligible artefactual acetaldehyde formation

A method is described for determination of acetaldehyde in blood by head space gas chromatography. The method utilizes sodium nitrite-sulfosalicylic acid as an inhibitor of the ethanol oxidizing systems by means of which the interference of ethanol is reduced considerably. The detection limit was 0.4 mumol/l, the recovery 101.5 +/- 5.2% and the coefficient of variation was 7.8% (1.5 mumol/1 acetaldehyde). There was no disappearance of acetaldehyde if the head space vials were kept at -20 degree C for 24 h. In the comparison study with the semicarbazide method our results were 0.7-4.1 mumol/l lower. The values for acetaldehyde in blood after ethanol ingestion (0.5 g/kg) by volunteers were 0.5-1.3 mumol/l.

High-performance liquid chromatography determination of dapsone, monoacetyldapsone, and pyrimethamine in filter paper blood spots

A high-performance liquid chromatography method for the simultaneous analysis of dapsone (DDS), the major metabolite of DDS, monoacetyldapsone (MADDS), and pyrimethamine (PYR) was modified for capillary blood samples obtained by finger prick and dried on filter paper. Limit of quantitation using 150 μl whole blood dried on filter paper was found to be 20 ng/ml for DDS and PYR and 15 ng/ml for MADDS (precision <15%). The clinically relevant concentrations of DDS are 50–2,000 ng/ml and for PYR 25–150 ng/ml. No interference from several drugs were observed. The accuracy of the filter paper method and the original whole-blood method was almost comparable. Standardization could therefore be obtained by the more simple whole-blood method. Dried filter paper samples stored at 19–22°C were stable for months and for 2 weeks stored at 35°C. The concentrations of simultaneously collected capillary blood and conventional venous blood samples correlated well. The present method using capillary blood dried on filter paper is reliable, simple, sensitive, and applicable in the field with limited technical facilities.

Effect of ethanol and pH on the adsorption of acetaminophen (paracetamol) to high surface activated charcoal, in vitro studies.

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 (50 g) 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 10:1 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 Langmuirs 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.

A reversed-phase high-performance liquid chromatography method for the determination of cotrimoxazole (trimethoprim/ sulphamethoxazole) in children treated for malaria.

A high-performance liquid chromatography (HPLC) method was developed for the simultaneous analysis of trimethoprim (TMP), sulphamethoxazole (SMX), and acetylsulphamethoxazole (AcSMX) in small amounts of blood. The method involved precipitation with 50 microL trichloracetic acid (1M) to 125 microL plasma or serum sample. 60 microL supernatant was added to 60 microL mobile phase, modified with 50microL 1 M sodium hydroxide/mL. The mobile phase consisted of 20% acetonitrile and 80% phosphate buffer adjusted to pH 6.15. Using 125 microL of the sample, limits of quantitation were 0.1 microg/mL for TMP, 1.0 microg/mL for SMX, and 1.0 microg/mL for AcSMX. The precision of the method was 2% to 11% over the range of concentrations tested, 0.5-30 microg/mL for TMP, 5-300 microg/mL for SMX, and 2.5-150 microg/mL for AcSMX, respectively. No interference with other commonly used drugs was observed. The method is rapid, simple, specific, and sensitive enough for pharmacokinetic studies. The small amount of blood required makes it suitable for pediatric patients. The method was used to analyze samples from Tanzanian children aged 6-59 months participating in a cotrimoxazole (TMP/SMX)/chloroquine randomized trial for the treatment of uncomplicated malaria. Venous blood samples from 68 children were collected 2 hours after the first dose of TMP/SMX (4 mg/kg TMP/20 mg/kg SMX at two divided doses for 5 days) and again at treatment day 4. Individual variations in plasma concentrations of TMP, SMX, and AcSMX were considerable. The mean and SEM plasma concentrations (g/mL) of TMP, SMX, and AcSMX 2 hours after the first treatment dose were 2.0 +/- 1.0 (range 0.5-6), 53 +/- 22 (range 24-146), and 13.5 +/- 12 (range 0-65), respectively. On the fourth day the attained plasma concentrations were not significantly different from samples collected after the first dose.