Capillary ion electrophoresis of endogenous anions and anionic adulterants in human urine.

Normal human urine contains many anions and cations. Ionic concentrations in urine have classically been determined by spectrophotometry of color reactions, flame emission spectrophotometry, atomic absorption spectrophotometry, high performance liquid chromatography, or potentiometry with ion-specific electrodes. Capillary ion electrophoresis (CIE) is a form of capillary electrophoresis which uses the differential electrophoretic mobility of ions to perform a separation of an ionic mixture. Various salts can be added to urine specimens to abnormally elevate ionic concentrations and interfere with either immunoassay urine drug screening procedures or gas chromatographic/mass spectrometric confirmation techniques. Application of CIE for the direct detection of endogenous anions and anionic adulterants in human urine specimens was the purpose of this investigation. CIE was performed using a Waters Quanta 4000 Capillary Electrophoresis System with either direct or indirect ultraviolet absorption detection at 254 nm. CIE of 30 random normal urine specimens and 21 urine specimens suspected of adulteration was performed. Duplicate aliquots were assayed by CIE and by colorimetric technique for nitrite. Sixteen specimens had elevated concentrations of nitrite and/or nitrate. The correlation coefficient between nitrite CIE and colorimetric results was 0.9895. Three specimens had detectable concentrations of chromate and were suspected of being adulterated with "Urine Luck," an adulterant found to contain chromate. Two specimens suspected of being adulterated with bleach were found to only contain chloride, sulfate, and phosphate. CIE is applicable to forensic analysis of urine anion concentrations. CIE can easily quantitate numerous endogenous anions and offers a method to detect and/or confirm anion adulteration of urine specimens.

Blocking swelling-activated chloride current inhibits mouse liver cell proliferation.

A non-transformed mouse liver cell line (AML12) was used to show that blocking swelling-activated membrane Cl- current inhibits hepatocyte proliferation. Two morphologically distinguishable cell populations exhibited distinctly different responses to hypotonic stress. Hypotonic stress (from 280 to 221 mosmol kg(-1)) to rounded, dividing cells activated an ATP-dependent, outwardly rectifying, whole-cell Cl- current, which took 10 min to reach maximum conductance. A similar anionic current was present spontaneously in 20 % of the dividing cells. Hypotonic stress to flattened, non-dividing cells activated no additional current. The Eisenman halide permeability sequence of swelling-activated anionic current in the dividing cells was SCN(-) > I(-) > Br(-) > Cl(-) > gluconate. Addition of either 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), tamoxifen or mibefradil inhibited swelling-activated anionic current. Hyperosmolarity by added sucrose inhibited the spontaneous anionic current in dividing cells. Added Cl- channel blockers NPPB (IC50 = 40 microM), DIDS (IC50 = 31 microM), tamoxifen (IC50 = 1.3 microM) and mibefradil (IC50 = 7 microM) inhibited proliferative growth of AML12 as determined by cell counts over 4 days or by protein accumulation over 2 days. Only the inhibitory effects of NPPB and mibefradil reversed with the drug washout. Hyperosmolarity by added sucrose (50 and 100 mM) also inhibited cell proliferation. Of the hydrophobic inhibitors neither NPPB at 40 microM nor tamoxifen at 1.3 microM, added for 48 h, reduced cellular ATP; however, DIDS at 31 microM significantly reduced cellular ATP with an equivalent increase in cellular ADP. We conclude that those membrane Cl- currents that can be activated by hypotonic stress are involved in mechanisms controlling liver cell growth, and that NPPB, tamoxifen and mibefradil at their IC50 for growth do not suppress the metabolism of mouse hepatocytes.

Iontophoresis of dexamethosone-phosphate into the equine tibiotarsal joint.

In human rehabilitation medicine, dexamethasone-phosphate is theoretically iontophoresed to localized subcutaneous tissue where conversion to dexamethasone occurs. This delivery system has recently been introduced into veterinary medicine for the same purpose. However, the pharmacokinetic justification for parenteral delivery of this prodrug remains undocumented. Utilizing iontophoretic methods that are relevant to both human and veterinary clinical practice, the present investigation compared injection and iontophoresis of dexamethasone-phosphate into the equine tibiotarsal joint, also known as the tarsocrual joint. The tibiotarsal joints of seven horses were injected with 4 mL of 6 mg/mL dexamethasone-phosphate. With a similar drug concentration and over the same application site, six different horses underwent simultaneous cathodic iontophoresis (4 mA, 40 min) or passive application (0 mA, 40 min) on contralateral limbs. Following all applications, tibiotarsal joint synovium was collected. Local venous blood samples were also collected from the iontophoretic and passive application sites for analysis of plasma drug concentrations. Because of the potential for conversion of dexamethasone-phosphate to dexamethasone, an extraction and analysis protocol was developed for both chemicals. The technique demonstrated a linear range of detection (0.39-12 microg/mL) and a capability for measuring both chemicals in plasma and synovium. Conversion of dexamethasone-phosphate to dexamethasone occurred during synovial incubation (37 degrees C) and following freeze-thaw cycles. In contrast to the measurable synovial concentrations of dexamethasone-phosphate (2.3 +/- 0.96 mg/mL) and dexamethasone (0.27 +/- 0.07 mg/mL) following injection, neither drug was detected in the synovium or the local venous blood following iontophoretic or passive applications. In conclusion, these results do not confirm iontophoretic or passive delivery of measurable dexamethasone-phosphate into the tibiotarsal joint using current clinical methods.

Topical absorption of isopropyl alcohol induced cardiac and neurologic deficits in an adult female with intact skin.

Topical exposure to isopropyl alcohol has been reported in the literature to be toxic if sufficient isopropyl alcohol is absorbed (1-5). A clinical case is reported where a 48-y-old female presented with multiple unexplained cardiac and neurological deficits. The woman had developed the deficits over a 6-mo period in which she had been soaking towels with isopropyl alcohol and applying then to her skin overnight to ease arm pain she was experiencing. Cessation of the isopropyl alcohol exposure resolved her deficits within 3 d. A controlled repeat dermal exposure to isopropyl alcohol under clinical observation reproduced the deficits noted with corresponding serum and urine concentrations of isopropyl alcohol and acetone. Cessation of topical isopropyl alcohol exposure lead to subsequent resolution of all toxicities.

Ketoprofen tissue permeation in swine following cathodic iontophoresis.

BACKGROUND AND PURPOSE: Pharmacokinetic assessment of drug tissue permeation following iontophoresis is limited. The depth of ketoprofen tissue permeation following cathodic iontophoresis (4 mA, 40 minutes) and the stereoselectivity of drug delivery were examined in this study. SUBJECTS: Ketoprofen (750 mg) was iontophoresed onto one porcine medial thigh, with passive drug permeation conducted on the other thigh. METHODS: Skin, subcutaneous fascia, and muscle biopsies from the drug delivery sites were harvested and stored separately, and the "R" and "S" ketoprofen enantiomers were determined. Results. Iontophoretic and passive applications yielded equivalent total ketoprofen concentrations in the skin and fascia. In contrast, multivariate analysis demonstrated that the ketoprofen concentration in the first centimeter of muscle following iontophoresis was greater than the drug concentration in the deeper underlying muscle layers and greater than that delivered to any muscle layer following passive delivery. No transcutaneous stereoselective delivery) of ketoprofen was detected. CONCLUSION AND DISCUSSION: Compared with passive delivery, iontophoresis enhances nonstereoselective ketoprofen permeation into the fascia-muscle interface. With delivery to deeper tissue sites, however, there is no apparent enhancement over passive application.

Capillary ion analysis of lithium concentrations in biological fluids and tissues of Poecilia (teleost).

Capillary ion analysis (CIA) is a form of capillary electrophoresis that uses the differential electrophoretic mobility of ions to perform a separation of an ionic mixture. Application of this technique for detection of lithium concentrations in plasma and tissues of Poecilia was the purpose of this investigation. CIA was performed using a 75 microm ID x 60 cm length fused-silica capillary and a run electrolyte of 67.7 mg hydroxyisobutyric acid (HIBA), 52.8 mg 18-crown-6-ether and 64 microL UV-CAT-1 reagent (4-methylbenzylamine) in a volume of 100 mL water (18 (M)omega) with a voltage of 20 kV using ultraviolet absorption detection at 214 nm. Migration times were: potassium, 2.98 min; calcium, 3.48 min; sodium, 3.60 min; barium (internal standard), 4.15 min and lithium, 4.26 min. Lithium and barium migration times were stable and reproducible. Correlation coefficients (r) between peak area ratios of lithium/barium for concentrations ranging from 0.1 to 2.0 mM were from 0.976 to 0.996. Coefficients of variation (CV) for lithium concentrations ranged from 4.07 to 15.71% between days and 4.38 to 7.76% within-day. Application of this methodology for determination of lithium concentrations in the plasma, brains and livers of fish dosed with lithium for 23 days are presented. CIA is applicable to analysis of lithium concentrations in biological fluids and tissues of fish.

A fatal drug interaction between clozapine and fluoxetine.

A case is presented of a fatal drug interaction caused by ingestion of clozapine (Clozaril) and fluoxetine (Prozac). Clozapine is a tricyclic dibenzodiazepine derivative used as an "atypical antipsychotic" in the treatment of severe paranoid schizophrenia. Fluoxetine is a selective serotonin reuptake inhibitor used for the treatment of major depression. Clinical studies have proven that concomitant administration of fluoxetine and clozapine produces increased plasma concentrations of clozapine and enhances clozapine's pharmacological effects due to suspected inhibition of clozapine metabolism by fluoxetine. Blood, gastric, and urine specimens were analyzed for fluoxetine by gas chromatography/mass spectrometry (GC/MS) and for clozapine by gas-liquid chromatography (GLC). Clozapine concentrations were: plasma, 4.9 micrograms/mL; gastric contents, 265 mg; and urine, 51.5 micrograms/mL. Fluoxetine concentrations were: blood, 0.7 microgram/mL; gastric contents, 3.7 mg; and urine 1.6 micrograms/mL. Norfluoxetine concentrations were: blood, 0.6 microgram/mL, and none detected in the gastric contents or urine. Analysis of the biological specimens for other drugs revealed the presence of ethanol (blood, 35 mg/dL; vitreous, 56 mg/dL; and urine 153 mg/dL) and caffeine (present in all specimens). The combination of these drugs produced lethal concentrations of clozapine and high therapeutic to toxic concentrations of fluoxetine. The deceased had pulmonary edema, visceral vascular congestion, paralytic ileus, gastroenteritis and eosinophilia. These conditions are associated with clozapine toxicity. The combined central nervous system, respiratory and cardiovascular depression of these drugs was sufficient to cause death. The death was determined to be a clozapine overdose due to a fatal drug interaction.

Tissue extraction and high-performance liquid chromatographic determination of ketoprofen entantiomers.

Local transcutaneous delivery of non-steroidal anti-inflammatory drugs avoids gastrointestinal side effects and concentrates drugs in the intended tissues. An extraction and HPLC method was developed for ketoprofen in skin, fascia and muscle. Tissue samples were homogenized in NaHCO3. After methylene chloride removal of lipids, the aqueous layer was acidified with HCl and back extracted into isooctane/isopropanol. Ketoprofen was derivatized with ethylchloroformate/S-(-)-alpha-phenylethylamine in triethylamine, then detected by HPLC. Ketoprofen recovery was linear (1-33 microg/g) and was detected in these tissues following in vivo cathodic iontophoresis (160 mA*min). This represents the first non-radioactive method for determination of ketoprofen in tissues following transcutaneous iontophoresis.

Capillary ion analysis of potassium concentrations in human vitreous humor.

Capillary ion analysis (CIA) is a form of capillary electrophoresis which uses the differential electrophoretic mobility of ions to perform a separation of an ionic mixture. Application of this technique for direct detection of potassium concentrations in human vitreous humor was the purpose of this investigation. CIA was performed using a Waters Quanta 4000 Capillary Electrophoresis System with a 745 Data Module using a 75 microm x 60 cm capillary and a run electrolyte of 67.7 mg hydroxyisobutyric acid (HIBA), 52.8 mg 18-crown-6-ether and 64 microL UV-CAT-1 reagent (4-ethylbenzylamine) in a volume of 100 mL water (18 Mohm) with a voltage of 20 kV using ultraviolet absorption detection at 214 nm. Migration times were: ammonium ion, 2.86 min; potassium, 3.24 min; calcium, 3.84 min; sodium, 3.98 min; barium (internal standard), 4.68 min; and lithium, 4.79 min. Correlation coefficients (r) between peak area ratios and concentration ranges of 2.5-144 mmole/L (100-1000 ppm) were from 0.9855 to 0.9999. Coefficients of variation (CV) ranged from 1.45 to 13.8% between days and from 1.38 to 9.43% within-day. Application of this methodology to twenty-five vitreous humor specimens from forensic cases was compared to analysis by ion-specific electrode for potassium concentration. Comparison of CIA to ion-specific electrode analysis of vitreous humor potassium concentrations revealed a correlation coefficient of 0.9642. CIA is applicable to forensic analysis of potassium concentration in forensic vitreous humor specimens. Quantitation of numerous cation concentrations is possible by direct CIA of vitreous humor.

The effect of indomethacin administration on the splenic changes induced by estradiol supplementation in ovariectomized New Zealand white rabbits.

In an effort to elucidate the mechanism by which indomethacin (IN) lessens the stimulatory effect of estradiol (E2) on rabbit splenic red pulp macrophages (RPMs), 39 female New Zealand White rabbits were divided into 10 groups: ovariectomized (OVX) and OVX/IN at 0.1 and 5.0 mg/kg body weight (bw)/day; sham OVX (SOVX) and SOVX/IN at 0.1 and 5.0 mg/kg bw/day; OVX/25 mg E2 and OVX/25 mg E2/IN at 0.1 and 5.0 mg/kg bw/day; and intact control. Changes in RPM population in response to treatment were measured using a 0-4 histologic grade. Estradiol treatment resulted in increased RPM grade when compared to the OVX groups. Indomethacin addition lowered mean RPM grade in the SOVX/IN 5.0 group when compared to its E2 control group. Indomethacin administration had no significant effect on levels of prostaglandin E2 in spleen, urine, or blood. Hematocrits were reduced in both OVX and OVX/E2 groups; this decrease was exacerbated by the high IN dose. In summary, the results from this study suggest that the effect of IN on E2-induced RPM activation may be mediated through a nonprostaglandin pathway. The observed hematocrit changes are possibly the result of direct action of IN and E2 on erythrocytes, resulting in their accelerated clearance from the circulation by splenic RPM.

In vitro effects of oestradiol and indomethacin on rabbit erythrocyte fragility characteristics.

An in vitro study was conducted to determine whether indomethacin (IN) and oestradiol (E(2)) induced decreases in rabbit haematocrit may be related to their effect on erythrocyte fragility (EF). Aliquots of treated rabbit whole blood were assayed as control, IN (9.6 mug/ml), E(2) (500 pg/ml) and IN + E(2), for changes in EF. Osmotic (OF) and mechanical (MF) fragility in eight experimental replicates were evaluated under approximate physiological conditions by measurement of haemoglobin release. Samples were assayed immediately after drug addition and again 4 hr after incubation at 39.5 degrees C. OF results showed a significant increase in 50% haemolysis between final IN and IN + E(2) values when compared with their initial values and with controls. OF haemolysis dispersion was increased over time by IN and IN + E(2). MF increased with IN, E(2) and IN + E(2) versus their initial values and the controls. Although the increase in MF from IN was greater than that from E(2), the MF from IN + E(2) was not greater than that from IN alone. The IN induced increases in both OF and MF indicate a difference in degree of interaction with the erythrocyte from that of E(2), which affected only MF and the effect of which was neither additive nor synergistic with that of IN.

Mathematical modeling of the osmotic fragility of rabbit red blood cells.

The osmotic fragility (OF) test is used to determine the extent of red blood cell hemolysis (RBCH) produced by osmotic stress. RBCH is dependent upon cell volume, surface area, and functional integrity of cell membranes. The variation of cell lysis with stress reflects underlying cell subpopulations and their membranes' cytoskeletal functionality. OF was determined on blood from New Zealand white rabbits. The dependence of RBCH on NaCl concentration ([NaCl]) was determined spectrophotometrically by measuring absorbance (Abs) from hemoglobin release at 545 nm. Abs data were fitted to the equation Abs = p3 erfc(([NaCl]--p1)/p2) where p3 reflects maximum RBCH, p1 measures the [NaCl] at 50% RBCH, and p2 shows the dispersion in [NaCl] producing the RBCH. Parameter values for control blood were p1 = 0.4489 +/- 0.0016; p2 = 0.0486 +/- 0.0016; and p3 = 0.4366 +/- 0.0022. Addition of indomethacin (9.6 micrograms/mL) produced an increased fragility in the RBC's characterized by increased values of p1 and p2. Normalization of the data to p3 did not change the values of p1 or p2. Our equation satisfactorily describes the variation in RBCH as a function of [NaCl]. The parameters of the equation can be used to quantitatively characterize Abs/[NaCl] data and compare pharmacological, toxicological, and pathological effects on the OF of RBC's.

Application of micellar electrokinetic capillary chromatography to forensic analysis of barbiturates in biological fluids.

Micellar electrokinetic capillary chromatography (MECC) is a form of capillary zone electrophoresis. Addition of a surfactant produces micelles in an aqueous/organic buffer. Separation of drugs is obtained via differences in the electrophoretic mobilities of the analytes within the capillary, resulting from their electrophoretic velocity and the electroosmotic flow of the buffer in a given electric field. The migration order is determined by the differential partitioning of the drugs between the micelles and the aqueous/organic phase. Barbiturates were extracted from various biological fluids at pH 4.5 with TOXI-TUBES B. MECC analyses were performed using a Waters Quanta 4000 Capillary Electrophoretic System with a 745 Data Module with a 75 microns x 60 cm capillary and an aqueous/organic buffer of 85% 10 mM borate, 10 mM phosphate, 100 mM sodium dodecyl sulfate and 15% acetonitrile at a pH of 8.5 with a voltage of 20 kV using ultraviolet absorption detection at 214 nm. Migration times were: phenobarbital, 7.78 min.; butalbital, 8.01 min.; butabarbital, 8.23 min.; mephobarbital (internal standard), 8.88 min.; amobarbital, 9.41 min.; pentobarbital, 10.03 min. and secobarbital, 10.79 min. Correlation coefficients (r) between peak areas and concentration ranges of 3 to 60 micrograms/mL were from 0.964 to 0.999. Coefficients of variation (CV) ranged from 2.6 to 8.6% between days and 2.3 to 9.8% within day. Application of this methodology to four forensic cases of butalbital intoxication detected concentrations of 0.7 to 12.7 micrograms/mL in blood; 0.8 to 1.9 micrograms/mL in vitreous humor and 1.5 to 7.6 micrograms/mL in urine. MECC is applicable to forensic analysis of barbiturates extracted from biological fluids.

Investigation of the influence of acetylsalicylic acid on the steady state of long-term therapy with theophylline in elderly male patients with normal renal function.

The risk inherent in the clinical control of patients with theophylline is widely recognized. Elderly patients may present an additional risk because of altered pharmacokinetics and the use of concomitant medication. Acetylsalicylic acid has been proposed for primary and secondary prevention of myocardial infarction and possible strokes. This investigation was undertaken to determine if concomitant administration of acetylsalicylic acid in elderly patients would alter steady-state levels of theophylline. A population of smoking male patients older than 60 years of age under long-term control of chronic obstructive pulmonary disease (COPD) with theophylline were evaluated for a baseline period of 3 days. Serum levels were measured at 6:00 AM and 6:00 PM. An enteric-coated acetylsalicylic acid preparation, 650 mg by mouth, was added to the daily slow-release theophylline, 6:00 AM hour dose regimen for 4 weeks. The serum levels of theophylline and salicylates were measured at 6:00 PM after dosing and at 6:00 AM the following day, at weekly intervals for 4 weeks. Urine specimens collected before administration of medication at 6:00 AM were analyzed for salicylates to further confirm dosage compliance. All volunteers continued to be clinically controlled throughout the treatment period and no symptoms of either overdose or underdose of either medication occurred. Plateau or trough theophylline serum levels did not change significantly during the salicylate treatment period. Salicylate serum levels did show during treatment self-induced metabolism. It is concluded that in elderly male patients, a daily concomitant therapeutic salicylate regimen does not alter steady-state serum theophylline levels and therefore does not per se necessitate the assay of theophylline blood levels in elderly patients.

Pharmacokinetics and bioavailability of the RRR and all racemic stereoisomers of alpha-tocopherol in humans after single oral administration.

The plasma and red blood cell pharmacokinetics and bioavailability of the natural source (RRR, d) and all racemic (all rac, dl) stereoisomers of alpha-tocopherol were studied in 12 men in a double-blind randomized crossover study. Subjects were administered two 400-mg soft-gelatin capsules of either RRR or all rac alpha-tocopherol. Plasma alpha-tocopherol concentrations were determined by high-performance liquid chromatography at various time intervals for up to 96 hours postadministration. Pharmacokinetic modeling of the data showed that alpha-tocopherol was absorbed after a 2 to 4 hour lagtime and maximum plasma concentration occurred from 12 to 14 hours postadministration. There were no significant differences in the Ka, t1/2 a, beta, or t1/2 beta between RRR and all rac. Mean plasma alpha-tocopherol concentrations were greater for RRR than all rac from 10 to 96 hours postadministration and significantly greater at 24 hours (P < .05). The red blood cell alpha-tocopherol concentration from the RRR preparation was significantly greater than from the all rac preparation from 24 to 96 hours postadministration with Cmax for RRR (4.8 micrograms/mL) significantly greater than for all rac (4.0 micrograms/mL, P < .05). The RRR AUC0-96 for both plasma and red blood cells were significantly greater than the all rac AUC0-96 (P < .05) indicating a greater bioavailability of RRR versus all rac alpha-tocopherol. This difference in overall bioavailability was apparently not due to a single pharmacokinetic component.

The effect of ibuprofen on ethanol concentration and elimination rate.

Pursuant to a recent driving under the influence (DUI) case, a medical study of six subjects was cited reporting that ibuprofen causes a decrease in the maximum rate of elimination of ethanol. Such a drug interaction is of significant forensic science interest and warrants further examination. This study investigates the effect of ibuprofen on ethanol elimination rate and ethanol concentration in nineteen volunteers. Volunteer subjects were randomly assigned to two groups administered either a placebo followed by ethanol or ibuprofen followed by ethanol. Subjects served as their own control. Blood ethanol concentrations were monitored every 30 to 60 min for up to 4 h with Intoximeter 3000 instruments. A blood sample was drawn at the final Intoximeter test and analyzed for ethanol and ibuprofen by gas chromatography and mass spectrometry, respectively. The mean elimination rate (+/- SD) as calculated using Widmark's elimination factor was 0.018 +/- 0.006 g/dL for ethanol and 0.017 +/- 0.007 g/dL/h for ethanol with ibuprofen. Mean ethanol concentrations (g/dL +/- SD) were: 0.095 +/- 0.026 (ethanol) and 0.095 +/- 0.033 (ethanol and ibuprofen) at 30 min; 0.077 +/- 0.026 (ethanol) and 0.075 +/- 0.031 (ethanol and ibuprofen) at 150 min; and 0.089 +/- 0.025 (ethanol) and 0.087 +/- 0.030 (ethanol and ibuprofen) overall. There was no statistically significant affect of ibuprofen on either the peak blood ethanol concentration or the ethanol elimination rate (p less than or equal to 0.001). These results reveal no evidence of a significant ethanol-ibuprofen interaction.

The toxicokinetics of 1,3-butylene glycol versus ethanol in the treatment of ethylene glycol poisoning.

Ethylene glycol (EG) is a toxic chemical found in antifreeze and heat exchangers. Standard therapy for EG intoxication in administration of ethanol (ETOH) to inhibit its metabolism by alcohol dehydrogenase (ADH). Studies indicate 1,3-butylene glycol (BG) binds to ADH more efficiently than EG and is orally less toxic than EG or ETOH. Male rats were divided into 5 groups of 6 animals. Groups received by oral intubation a single dose of EG (32 mmole/kg), BG (39 mmole/kg) initially and every 6 h up to 72 h, ETOH (39 mmole/kg) initially and every 6 h up to 72 h, or EG initially and then either BG or ETOH every 6 h up to 72 h. Administration of ETOH produced hepatotoxicity and pulmonary pathology as indicated by changes in clinical chemistry, urinalysis, and histopathology, while BG did not. Neither ETOH nor BG produced any apparent nephrotoxicity. ETOH produced ataxia, lethargy and central nervous system depression while BG did not. BG produced a higher concentration of urinary EG indicating a better inhibition of ADH metabolism of EG. Ethanol produced a higher EG blood concentration than BG. Ethanol's higher EG blood concentration may be partially attributed to dehydration and a decreased urine output as well as inhibition of ADH metabolism. Ethanol produced mortality in all animals prior to 72 h. The EG/ETOH combination produced mortality more quickly due to additive toxicity of the combination. Lack of any significant toxicity produced by BG and the production of significant toxicities by ETOH indicates that BG is potentially a better antidote than ETOH.

Poisoning from oral ingestion of carbofuran (Furadan 4F), a cholinesterase-inhibiting carbamate insecticide, and its effects on cholinesterase activity in various biological fluids.

A case is presented of a fatal ingestion of Furadan (carbofuran), a cholinesterase-inhibiting carbamate insecticide. A 26-year-old white male was found dead with a partially filled 1-gal (3.8-L) container of Furadan 4F insecticide-nematocide (44.9% carbofuran). The individual had ingested approximately 345 mL of the mixture. Analysis of cholinesterase activity in various biological fluids was performed spectrophotometrically using propionylthiocholine and 5,5'-dithiobis-2-nitrobenzoic acid [Sigma Diagnostics, cholinesterase procedure No. 422 (PTC)] which was measured at 405 nm and 30 degrees C in a Gilford Stasar III Spectrophotometer. The cholinesterase activities were as follows: plasma, 245 units (U)/L (93% inhibition/7% normal activity); serum, 208 U/L (95.3% inhibition/4.7% normal activity); whole blood, 297 U/L (92.8% inhibition/7.2% normal activity); erythrocytes, 58 U/L (99% inhibition/1% normal activity); vitreous humor, 7 U/L; and bile, 148 U/L. Carbofuran was detected in the blood and gastric contents by thin-layer chromatography. No alcohol or other drugs were detected in the blood, urine, or gastric contents. Ingestion of the carbofuran produced acute visceral congestion and pulmonary edema. Death was caused by anoxia due to respiratory paralysis produced by cholinesterase inhibition from Furadan (carbofuran) ingestion.