American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee.

Fomepizole (4-methylpyrazole, 4-MP, Antizol) is a potent inhibitor of alcohol dehydrogenase that was approved recently by the US Food and Drug Administration (FDA) for the treatment of ethylene glycol poisoning. Although ethanol is the traditional antidote for ethylene glycol poisoning, it has not been studied prospectively. Furthermore, the FDA has not approved the use of ethanol for this purpose. Case reports and a prospective case series indicate that the intravenous (i.v.) administration of fomepizole every 12 hours prevents renal damage and metabolic abnormalities associated with the conversion of ethylene glycol to toxic metabolites. Currently, there are insufficient data to define the relative role of fomepizole and ethanol in the treatment of ethylene glycol poisoning. Fomepizole has clear advantages over ethanol in terms of validated efficacy, predictable pharmacokinetics, ease of administration, and lack of adverse effects, whereas ethanol has clear advantages over fomepizole in terms of long-term clinical experience and acquisition cost. The overall comparative cost of medical treatment using each antidote requires further study.     

Role of fomepizole in the management of ethylene glycol toxicity

OBJECTIVE: To systematically review English-language articles on fomepizole administration in patients with ethylene glycol poisoning. DATA SOURCES: MEDLINE, EMBASE, Current Contents, and PubMed. Search terms were fomepizole, 4-methylpyrazole, and ethylene glycol. The search was supplemented with a bibliographic review of all relevant articles. STUDY SELECTION: All published reports of fomepizole administration in patients with ethylene glycol poisoning were reviewed, irrespective of study design. We identified one clinical trial and subsequent pharmacokinetic study, one case series, and 13 case reports. RESULTS: Fomepizole has been investigated in 70 patients in open, unblinded studies. Most patients received an intravenous loading dose, with subsequent variable maintenance doses every 12 hours until plasma ethylene glycol levels became undetectable. Additional hemodialysis treatment generally was administered when patients had renal insufficiency or ethylene glycol levels above 50 mg/dl. Many patients had detectable ethanol levels either because of coadministration or as a result of adjunctive treatment at a referring center. Poorer patient outcomes, such as death and renal insufficiency, were associated with later clinical presentation time after ingestion. At therapeutic fomepizole levels (> 8.6 mg/ml), the half-life of ethylene glycol was prolonged to over 19 hours. Fomepizole appeared to be well tolerated by most patients. CONCLUSION: Fomepizole is an effective alcohol dehydrogenase inhibitor that decreases production of ethylene glycol metabolites. Reduced mortality and morbidity are undetermined because of the small number of patients evaluated to date. Data on comparative efficacy of fomepizole versus ethanol and data on administration of fomepizole in children are limited.     

Ethylene glycol ingestion treated only with fomepizole

Introduction

Ethylene glycol is a widely used chemical that is capable of causing significant injury if ingested. Treatment for ethylene glycol poisoning typically includes basic supportive care, alcohol dehydrogenase inhibition, and hemodialysis. Recent data have suggested that hemodialysis may not be necessary for cases of ethylene glycol poisoning that can be treated with fomepizole as blocking therapy before acidosis or renal dysfunction develops.

Case Report

A 33-year-old man presented to the emergency department 1 hour after drinking approximately 1/2 gallon of ethylene glycol antifreeze and an unknown quantity of beer. On arrival he was mildly inebriated but otherwise displayed no other features of ethylene glycol poisoning. Fomepizole therapy was initiated and initial laboratory studies later revealed an osmol gap of 157 mOsm and an ethylene glycol concentration of 706 mg/dL. Nephrology and toxicology services were consulted. Over the next 3 days, fomepizole therapy was continued while the patient’s acid-base status and renal function were closely monitored. No evidence of acid-base abnormalities or renal impairment was ever observed and the patient was discharged to psychiatric care on the fourth hospital day.

Discussion

This report describes the case of a patient who presented soon after a massive ingestion of ethylene glycol with very high serum concentrations. He was successfully treated using fomepizole and basic supportive care. Our patient developed neither renal insufficiency nor metabolic acidosis. His concomitant ethanol consumption, early presentation, and treatment likely contributed to his favorable outcome. This case report underscores the effectiveness of supportive care and fomepizole in the treatment of ethylene glycol poisoning.     

American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning

EPIDEMIOLOGY: Almost all cases of acute methanol toxicity result from ingestion, though rarely cases of poisoning have followed inhalation or dermal absorption. The absorption of methanol following oral administration is rapid and peak methanol concentrations occur within 30-60minutes. MECHANISMS OF TOXICITY: Methanol has a relatively low toxicity and metabolism is responsible for the transformation of methanol to its toxic metabolites. Methanol is oxidized by alcohol dehydrogenase to formaldehyde. The oxidation of formaldehyde to formic acid is facilitated by formaldehyde dehydrogenase. Formic acid is converted by 10-formyl tetrahydrofolate synthetase to carbon dioxide and water. In cases of methanol poisoning, formic acid accumulates and there is a direct correlation between the formic acid concentration and increased morbidity and mortality. The acidosis observed in methanol poisoning appears to be caused directly or indirectly by formic acid production. Formic acid has also been shown to inhibit cytochrome oxidase and is the prime cause of ocular toxicity, though acidosis can increase toxicity further by enabling greater diffusion of formic acid into cells. FEATURES: Methanol poisoning typically induces nausea, vomiting, abdominal pain, and mild central nervous system depression. There is then a latent period lasting approximately 12-24 hours, depending, in part, on the methanol dose ingested, following which an uncompensated metabolic acidosis develops and visualfunction becomes impaired, ranging from blurred vision and altered visual fields to complete blindness. MANAGEMENT: For the patient presenting with ophthalmologic abnormalities or significant acidosis, the acidosis should be corrected with intravenous sodium bicarbonate, the further generation of toxic metabolite should be blocked by the administration of fomepizole or ethanol and formic acid metabolism should be enhanced by the administration of intravenous folinic acid. Hemodialysis may also be required to correct severe metabolic abnormalities and to enhance methanol and formate elimination. For the methanol poisoned patient without evidence of clinical toxicity, the first priority is to inhibit methanol metabolism with intravenous ethanol orfomepizole. Although there are no clinical outcome data confirming the superiority of either of these antidotes over the other, there are significant disadvantages associated with ethanol. These include complex dosing, difficulties with maintaining therapeutic concentrations, the need for more comprehensive clinical and laboratory monitoring, and more adverse effects. Thus fomepizole is very attractive, however, it has a relatively high acquisition cost. CONCLUSION: The management of methanol poisoning includes standard supportive care, the correction of metabolic acidosis, the administration of folinic acid, the provision of an antidote to inhibit the metabolism of methanol to formate, and selective hemodialysis to correct severe metabolic abnormalities and to enhance methanol and formate elimination. Although both ethanol and fomepizole are effective, fomepizole is the preferred antidote for methanol poisoning.     

Butoxyethanol ingestion with prolonged hyperchloremic metabolic acidosis treated with ethanol therapy

BACKGROUND: Severe toxic ingestions of butoxyethanol (CAS No. 111-76-2) are rare despite the prevalence of this glycol ether in products such as glass and surface cleaners. Manifestations of acute butoxyethanol toxicity include metabolic acidosis, hemolysis, hepatorenal dysfunction, and coma, but vary widely in reported cases. Furthermore, the optimal therapeutic approach is not yet established. Much of the toxicity of butoxyethanol has been ascribed to its aldehyde and acid metabolites which are similar to those produced by oxidative metabolism of methanol and ethylene glycol. Although the roles of alcohol dehydrogenase inhibition with ethanol or fomepizole and hemodialysis are clear in the case of toxic ingestions of methanol and ethylene glycol, they remain poorly defined for butoxyethanol poisoning. CASE REPORT: We report the case of a 51-year-old female who ingested up to 8 ounces of Sanford Expo White Board Cleaner (butoxyethanol and isopropanol). She developed prolonged hyperchloremic metabolic acidosis and mental status depression and was treated with ethanol therapy but not hemodialysis. This patient recovered without apparent sequelae. The kinetics of butoxyethanol metabolism in this case are described and the potential therapeutic options are discussed.     

Survival and complete recovery after severe acute ethylen glycol poisoning — a case report

Early signs of acute ethylene glycol (EG) poisoning are similar to ethanol intoxication. However, such signs of EG poisoning are followed by severe metabolic acidosis, increased anion gap, neurological and renal dysfunction, and, without adequate therapy, up to 40% mortality. Early recognition and treatment with intravenous ethanol or fomepizole and bicarbonate, renal replacement therapy, and supportive measures are the key elements of survival.     

急性乙二醇中毒3例报告及文献回顾

乙二醇为防冻剂的主要成分。乙二醇主要在肝脏内先后代谢为羟乙醛、乙醇醛、乙醇酸及草酸。这些代谢特可导致代谢性酸中毒。典型临床表现通常为3个阶段：第1阶段在摄入后12h内，乙二醇致中枢神经系统抑制；第2阶段在摄入12～24h后，出现代谢性酸中毒和心肺疾病；第3阶段在摄入后24～72h。出现肾小管坏死和肾衰竭。乙二醇致死量为1．4-1．6ml／kg[成人（70kg）约为100m1]。一旦怀疑乙二醇中毒，应尽快测定乙二醇和乙醇酸血浓度明确诊断。中毒治疗原则包括早期及时洗胃，给予乙醇或甲吡唑解毒剂，血液透析，碳酸氢钠vitB6等。大多数乙二醇中毒患者经早期诊断治疗后可恢复正常。本文报告3例急性乙醇中毒，3例患者均为男性（48岁），每人服用防冻液约为150ml。2倒出现头痛有，1例出现上腹不适、兴奋、躁动。3倒患者在摄入乙醇后12～18h出现代谢性酸中毒，24h出现血尿。经洗胃和血液透析，给予法莫替丁40mg，10％葡萄糖酸钙20ml。4％碳酸氢钠静脉注射，38％白酒200ml口服。2倒治愈，1例于摄入乙二醇后29h死亡。     

Massive Ethylene Glycol Ingestion Treated with Fomepizole Alone—A Viable Therapeutic Option

Fomepizole is used to treat and prevent toxicity from ethylene glycol poisoning. Treatment with fomepizole without hemodialysis in massive ethylene glycol ingestion has been rarely reported in the literature; however, published literature and practice guidelines recommend considering dialysis for ethylene glycol levels >50 mg/dL. We report a case of massive ethylene glycol ingestion resulting in the highest serum ethylene glycol concentration in a patient without ethanol co-ingestion who was treated with fomepizole and was not hemodialyzed. A 48-year-old male presented to the emergency department after reportedly ingesting >1liter of antifreeze in an attempt at self-harm. He denied concomitant ethanol consumption. His initial presenting serum ethylene glycol level was 700 mg/dL, with normal renal function, and a metabolic acidosis with a high anion gap. One hour after presentation, he was started on intravenous fomepizole. Treatment with fomepizole continued until the patient's plasma ethylene glycol concentration was 16 mg/dL. His metabolic acidosis quickly resolved, he had no adverse reactions to the treatment, and his renal function remained normal. Ultimately, he was discharged to a psychiatric unit without sequelae. Published literature and practice guidelines suggests considering hemodialysis initiation in patients with an ethylene glycol level >50 mg/dL. This recommendation is anecdotally, rather than evidence, based. With the potential risks inherent in hemodialysis, our case provides evidence that treatment with fomepizole without hemodialysis appears to be a viable alternative option in patients with even extremely high plasma ethylene glycol concentrations as long as their renal function is intact.     

Incorporation of therapeutic interventions in physiologically based pharmacokinetic modeling of human clinical case reports of accidental or intentional overdosing with ethylene glycol.

Although occupational uses of the high production volume (HPV) chemical ethylene glycol (EG) have not been associated with adverse effects, there are case reports where humans have either intentionally or accidentally ingested large quantities of EG, primarily from antifreeze. The acute toxicity of EG can proceed through three stages, each associated with a different metabolite: central nervous system depression (ethylene glycol), cardiopulmonary effects associated with metabolic acidosis (glycolic acid), and ultimately renal toxicity (oxalic acid), depending on the total amounts consumed and the effectiveness of therapeutic interventions. A physiologically based pharmacokinetic (PBPK) model developed in a companion paper (Corley et al., 2005). Development of a physiologically based pharmacokinetic model for ethylene glycol and its metabolite, glycolic acid, in rats and humans. Toxicol. Sci., in press 2005) was refined in this study to include clinically relevant treatment regimens for EG poisoning such as hemodialysis or metabolic inhibition with either ethanol or fomepizole. Such modifications enabled the model to describe data from several human case reports, confirming the ability of the previous model to describe the pharmacokinetics of EG and its metabolite, glycolic acid, in humans across a broad range of doses and multiple exposure routes. By integrating the case report data sets with controlled studies in this PBPK model, it was demonstrated that fomepizole, if administered early enough in a clinical situation, can be more effective than ethanol or hemodialysis in preventing the metabolism of EG to more toxic metabolites. Hemodialysis remains an important option, however, if treatment is instituted after a significant amount of EG is metabolized or if renal toxicity has occurred.     

Treatment of severe pediatric ethylene glycol intoxication without hemodialysis

BACKGROUND: There is limited experience treating severe ethylene glycol poisoning in children without hemodialysis. The objective of this study was to describe the clinical course and outcome of severe pediatric ethylene glycol poisoning treated without hemodialysis. METHODS: Patient records were identified retrospectively by hospital discharge diagnosis (ICD-9 code) of ethylene glycol poisoning from 1999 through 2002 at a pediatric medial center. Patients with initial serum ethylene glycol concentrations less than 50 mg/dL or those who received hemodialysis were excluded. RESULTS: Six patients with an age range of 22 months to 14 years were admitted for treatment of ethylene glycol poisoning over a four-year period. Initial serum ethylene glycol concentrations ranged from 62 to 304 mg/dL (mean 174.0 mg/dL). The lowest-measured individual serum bicarbonates ranged from 4 to 17 mEq/L. All patients were initially admitted to intensive care. One patient received ethanol only, two patients received fomepizole only, and three patients received a loading dose of ethanol and then were converted to fomepizole therapy. None of the patients received hemodialysis. Treatment was continued until the serum ethylene glycol was less than 10 mg/dL. Metabolic acidosis resolved with intravenous fluid and supplemental bicarbonate within 24h. All patients had a normal creatinine upon presentation and at discharge. The mean length of stay in intensive care was 21h and on the ward was 33.7h. One episode of hypoglycemia occurred in a 22-month-old. All patients recovered without evidence of renal insufficiency or other major complications at discharge. CONCLUSION: Six pediatric patients with severe ethylene glycol intoxication and normal renal function were successfully treated without hemodialysis.     

Rapid determination of ethylene glycol and glycolic acid in biological fluids

Ethylene glycol poisoning of companion animals is a common occurrence and is sometimes involved in human intoxication. Ethylene glycol is of limited toxicity, but the metabolites including glycolic acid are responsible for poisoning. Conventional treatment has employed substances to prevent alcohol dehydrogenase from metabolizing the ethylene glycol, but to be effective, therapy must begin within hours of ethylene glycol consumption. We describe a rapid (10 min) analysis of biological fluids for ethylene glycol and glycolic acid using isocratic HPLC, a refractive index detector, and a Waters fast fruit juice analytical column.     

Considerations for the treatment of ethylene glycol poisoning based on analysis of two cases

The clinical picture as well as the principles of treatment in ethylene glycol poisoning differ with the time after ingestion. These time-related differences are illustrated by two case reports. During the first hours of ethylene glycol poisoning, the patient suffers from drunkenness, vomiting and somnolence due to the intoxicant effect of ethylene glycol on the central nervous system. In the following hours a poisoning with glycolate and oxalate develops, with increasing acidosis, renal and brain damage. A patient admitted within a few hours of an overdose, with no or only slight metabolic acidosis, may be successfully treated with ethanol. If the serum concentration of ethylene glycol is very high, hemodialysis may be deferred until the necessary staff and equipment are available. If the patient is admitted with severe metabolic acidosis, hemodialysis must be started immediately. The need for ethanol administration during hemodialysis merits reevaluation.     

Triethylene glycol poisoning treated with intravenous ethanol infusion

INTRODUCTION: Poisoning with triethylene glycol has been rarely reported in humans. Triethylene glycol is thought to be metabolized by alcohol dehydrogenase to acidic products resulting in the production of a metabolic acidemia. Triethylene glycol metabolism has previously been shown to be inhibited by fomepizole (4-methyl pyrazole) administration. We report a case of triethylene glycol ingestion, presenting with a metabolic acidemia, treated with intravenous ethanol administration. CASE REPORT: A 23-year-old female presented to the emergency department approximately 1-1.5 hours following ingestion of a gulp of triethylene glycol (99%) brake fluid with coma (GCS-3) and metabolic acidemia (pH 7.03, PCO2 44 mm Hg, Bicarbonate 11 mmol/L, anion gap 30 mmol/L, serum creatinine 90 mumol/L). She was intubated and given 100 mmol of intravenous sodium bicarbonate. An ethanol loading dose was administered followed by an infusion to maintain serum ethanol at 100 mg/dL. Acidemia gradually resolved over the next 8 hours and she was extubated 12 hours later. The ethanol infusion was continued for a total of 22 hours. There was no recurrence of acidemia. Serum ethanol, ethylene glycol, and methanol levels were nondetectable on presentation, as was serum salicylate. Urine drug of abuse screen and thin-layer chromatography revealed no other coingested substances. The patient was discharged to a psychiatric ward 36 hours postingestion. CONCLUSION: Pure triethylene glycol poisoning results in coma and metabolic acidemia and may be treated with alcohol dehydrogenase inhibitors such as ethanol.     

Ethylene glycol generates free radical metabolites in rats: an ESR in vivo spin trapping investigation

Ethylene glycol, best known as antifreeze, is most often ingested accidentally or as a substitute for alcochol by chronic alcohol abusers. The toxicity of ethylene glycol poisoning is due to its toxic metabolites rather than to ethylene glycol itself. In this study, electron spin resonance (ESR) spectroscopy has been used to study free radical generation in rats by acute ethylene glycol poisoning. The radical spin trapping technique was applied where the spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) reacted with free radical metabolites to form radical adducts in vivo. The radical adducts from ethylene glycol intoxication were detected in both the bile and urine samples of male Sprague-Dawley rats. The identification of the POBN-(.)[(13)C]ethylene glycol radical adduct provides for the first time direct ESR evidence for the generation of the ethylene glycol-derived radicals during acute intoxication by ethylene glycol, suggesting a new metabolic pathway. Simultaneous administration of alcohol dehydrogenase inhibitor 4-methylpyrazole with ethylene glycol resulted in an enhanced free radical generation in the bile. This report is the first evidence of ethylene glycol free radical metabolism in rats with acute ethylene glycol intoxication.     

Pyrazole and methylpyrazole for the treatment of 2-butoxyethanol poisoning

2-Butoxyethanol (BE) is a one member of a family of ethylene glycol monoalkyl ethers that are used in a variety of industrial and household products. The clinical features of human and animal BE intoxications mainly include metabolic acidosis, CNS depression and coma, hemolytic anemia, hematuria, and renal injury. It is believed that metabolic activation of BE to butoxyacetic acid (BAA) is responsible for these pathologic changes. The treatment of BE poisoning have been based on an inhibition of the metabolic pathway enzymes which convert BE to toxic metabolites. Therefore, a comparison was made between antidotal properties of pyrazole (PY) and 4-methylpyrazole (MP) in rats subcutaneously intoxicated with BE. It was found that both antidotes effectively protected animals against appearance of hemolytic anemia signs induced by BE. MP appears to be more efficient than PY. These data confirm the beneficial role of alcohol dehydrogenase (ADH) inhibitors in BE intoxication.     

Ethylene glycol intoxication: case report and pharmacokinetic perspectives

A 42-year-old man was brought to the emergency department with ethylene glycol intoxication. He was hemodynamically stable and had normal renal function. His serum ethylene glycol concentration was 284 mg/dl approximately 1 hour after ethylene glycol consumption. The patient was treated with fomepizole and forced diuresis. Elimination of ethylene glycol in this patient followed first-order pharmacokinetics. Elimination pharmacokinetics in this patient were compared with that in a patient who received fomepizole and hemodialysis. Fomepizole monotherapy can be given in patients without renal failure or metabolic acidosis even with serum ethylene glycol concentrations greater than 50 mg/dl. However, cost estimates based on this case suggest that if the patient is treated adequately with a single hemodialysis session and 24-hour hospitalization, then fomepizole monotherapy may be more expensive than the combination regimen of fomepizole and hemodialysis.     

Reversal of severe methanol-induced visual impairment: no evidence of retinal toxicity due to fomepizole.

Case Report: We report a case of methanol poisoning exhibiting complete recovery from severe visual impairment following treatment with ethanol, fomepizole, and hemodialysis. An adult male presented with central blindness after ingesting methanol. Initial visual acuity was <20/800 (finger counting at 1-2 feet) with retinal edema on fundoscopy, arterial pH 7.19, methanol 97 mg/dL (30 mmol/L), formate 14.3 mmol/L, and ethanol undetectable. The patient was treated with ethanol, then fomepizole intravenously (15, 10, then 5 mg/kg), and hemodialysis. Methanol metabolism was effectively blocked by fomepizole even after ethanol had been eliminated, and the patient recovered 20/20 vision by day 14 with normal fundoscopy. This case report confirms highly efficient inhibition of alcohol dehydrogenase by fomepizole, as well as demonstrate the safety of fomepizole in a patient already exhibiting end-organ retinal toxicity. The potential for fomepizole to inhibit retinol dehydrogenase, an isoenzyme of alcohol dehydrogenase essential to vision, did not appear to be clinically significant in this symptomatic methanol-poisoned patient.     

Ethylene glycol poisoning: experiences from an epidemic in Sweden.

In 1987 two lethal adult cases of accidental ethylene glycol poisoning were given spectacular attention in the Swedish mass media. This resulted in an epidemic of intentional ethylene glycol poisonings. In addition to six cases related to alcohol abuse, another 30 severe suicidal poisonings were reported to the Swedish Poison Information Centre in five months. The clinical course and outcome in these 36 severe cases are reviewed. The primary clinical manifestations were metabolic acidosis, CNS disturbances and kidney damage with circulatory failure in the most severe cases. Mortality was 17%. Fragmentation of the normal striation in heart cells was found in two of the fatal cases and severe brain damage in all fatal poisonings. The degree of acidosis but not the serum ethylene glycol level correlated with both kidney damage and outcome. Treatment included ethanol, correction of the metabolic acidosis and dialysis. Four patients with serum ethylene glycol concentrations of 10-20 mmol/L (620-1240 mg/L) but with no or minimal metabolic acidosis were treated with ethanol alone; none of these patients developed renal damage.     

Human skeletal muscle lactate dehydrogenase activity in the presence of some alcohol dehydrogenase inhibitors

Methanol, ethylene glycol and other alcohol intoxications are complicated by severe acidosis which could be caused by formation of metabolic acids and additionally lactic acid production. An increasing nicotinamide adenine dinucleotide reduced/nicotinamide adenine dinucleotide oxidized (NADH/NAD) ratio during alcohol biotransformation is responsible for the induction of lactic acidosis. The main purpose of the present paper was to evaluate the effect of 4-methylpyrazole, cimetidine, ethylenediaminetetraacetic acid disodium salt, ethanol and methanol on lactate dehydrogenase (E.C. 1.1.1.27) activity and to discuss this issue. The activity of the enzyme was determined spectrophotometrically, in vitro using human enzyme skeletal muscle homogenates. 4-Methylpyrazole, cimetidine and ethylenediaminetetraacetic acid disodium salt at concentrations 0.01, 0.1, 1.0 mM and 12.5, 25.0, 50.0 mM of ethanol and methanol were studied. Our results showed that cimetidine increased lactate dehydrogenase activity as compared to the control at all tested concentrations. Such activity was noted for 4-methylpyrazole at 0.1 mM and higher concentration. By contrast, no significant effect on lactate dehydrogenase activity in the presence of ethylenediaminetetraacetic acid disodium salt, methanol and ethanol was observed.     

Effect of selected alcohol dehydrogenase inhibitors on human hepatic lactate dehydrogenase activity - an in vitro study

Metabolic acidosis severely complicates methanol and ethylene glycol intoxications. Acidosis is caused by acid metabolites and can be intensified by lactate elevation. Lactate concentration depends on the NADH(2)/NAD ratio. Lactate dehydrogenase (LDH, E.C.1.1.1.27.) supplies more lactate when the level of NADH(2) is elevated. The aim of the study was to evaluate the effect of alcohol dehydrogenase (ADH) inhibitors and substrates: cimetidine, EDTA, 4-methylpyrazole (4-MP), Ukrain and ethanol on LDH activity. The activity of LDH was determined spectrophotometrically in human liver homogenates incubated with cimetidine, EDTA, 4-MP and Ukrain at concentrations of 2 x 10(-6), 10(-5) and 5 x 10(-5) m as well as ethanol at concentrations of 12.50, 25.00, 50.00 mm. The LDH activity was significantly increased by 10(-5) and 5 x 10(-5) m concentrations of cimetidine and 4-MP, and by all concentrations of ethanol. The most effective change of LDH activity of about 26% (P<0.01) was observed at the highest concentration of ethanol. Ukrain inhibited LDH activity at both concentrations, i.e. 10(-5) and 5 x 10(-5) m (P<0.05). However, EDTA did not significantly influence LDH activity. The data showed that ethanol and 4-MP, the main antidotes in methanol or ethylene glycol poisoning, may increase liver LDH activity - an undesirable effect during the therapy of patients intoxicated with these alcohols. On the other hand, the decrease of LDH activity in the presence of Ukrain is a promising finding but definitely requires further investigation.