Population pharmacokinetic modelling of valproic acid and its selected metabolites in acute VPA poisoning.

BACKGROUND: Valproic acid (VPA) is a first-line antiepileptic drug. It is used in the treatment of many different types of partial and generalized epileptic seizures. Though the clinical pharmacokinetics of VPA has been well defined, information about pharmacokinetics after overdoses is rare. The aim of this study was to try to build a population pharmacokinetic model that would describe the time course of VPA and its selected metabolites when the drug is ingested in an overdose situation. METHODS: Blood samples were collected during admission to the hospital and several times during treatment for poisoning (10 men and 10 women). The concentration of VPA and its metabolites were determined by liquid chromatography coupled with mass spectrometry. For population pharmacokinetic evaluation of VPA and its metabolites, the two-compartment-model was applied. RESULTS: The estimated doses of VPA taken ranged from 6 to 65g, while the time after ingestion ranged from 1 to 30h. Results showed that the ß-oxidation process exhibited Michaelis-Menten kinetics becoming saturated during acute intoxication. The same could not be said for the desaturation route. VPA therapy increased the Vmax for ß-oxidation by 59% while decontamination appeared to be of moderate efficacy lowering the F value by 34% on the average. CONCLUSIONS: None of the models perfectly described the experimental data. Important factors like the variable degree of protein binding by VPA could not be included in the models. The small number of subjects used in the study made the analysis of more covariates impossible.

Abnormal olanzapine toxicokinetic profiles--population pharmacokinetic analysis.

CONTEXT: Olanzapine is widely used in the treatment of schizophrenia and it is becoming more frequently responsible for overdoses. Standard pharmacokinetic models do not fit to the toxic concentration data. OBJECTIVE: The aim of present study is to investigate the reasons for an abnormal olanzapine plasma concentration time curve in the range of toxic concentrations. Two hypotheses were verified: entering the enterohepatic cycle, and drug deposition and its desorption from activated charcoal used for gastrointestinal decontamination. MATERIALS AND METHODS: One-hundred thirty-five plasma concentration data from 21 patients hospitalized for acute olanzapine poisoning were analyzed with the use of the population pharmacokinetic approach. A non-linear mixed-effects modeling approach with Monolix 4.3.1 was employed. RESULTS: A model assuming gallbladder emptying at irregular intervals was developed. Also, a model that describes desorption of olanzapine from the charcoal surface, in which the dose is divided into two absorbed fractions, was constructed. The analysis has found gastrointestinal decontamination and previous olanzapine treatment, as the significant covariates for toxicokinetic parameters of olanzapine. CONCLUSION: Our study provides interesting models for investigation of toxic concentration of olanzapine, which may also be used as the basis for further model development for other drugs as well. The investigated population was not large enough to reliably confirm any of the proposed models. It would be well worth continuing this study with more substantial data. Also, any additional information about olanzapine metabolite concentration could be vital.

[Laboratory investigations in acute olanzapine poisonings]. / Badania laboratoryjne w ostrych zatruciach olanzapina.

BACKGROUND: Olanzapine is an atypical antipsychotic with multireceptor affinity and different pharmacological effects, which can result with abnormalities in laboratory investigations. AIM OF THE STUDY: To assess the nature and frequency of laboratory tests abnormalities in patients with an acute olanzapine poisoning. MATERIAL: 26 adult cases (mean age 37.7 +/- 15.3 years) of an acute olanzapine poisoning (serum level above 100 ng/mL). Group consisted of 11 men and 13 women, but 1 man and 1 woman were poisoned twice. METHODS: Prospective analysis of the following laboratory parameters: complete blood count (CBC), coagulation tests (APTT, INR), serum concentration of sodium, potassium, chlorides, glucose, BUN, creatinine and bilirubin, serum activity of AST, ALT, GGTP and CPK, urinalysis. RESULTS: The most common laboratory abnormalities in the study group were: hyperglycaemia (96%), hyper-prolactinaemia (83%), elevated CPK (80%), hypokalaemia (75%), hyperbilirubinaemia (60%), leukocytosis (55%). Less frequent parameters were: elevated AST (20%), hyponatraemia (15%), elevated ALT(10%) and thrombocytopenia (5%). The onset of some parameters was as follows: 1st day of hospitalization hyperglycaemia, leukocytosis and hypokalaemia, 2nd - hyperbilirubinaemia and elevated CPK, and 3rd - hyperprolactinaemia. CONCLUSIONS: In acute olanzapine poisonings: (1) muscle and liver injury, serum glucose and electrolytes abnormalities, and changes in CBC can be present; (2) the valuable parameters for the monitoring of the course of poisonings are: serum activity of CPK and transaminases (AST, ALT), serum level of bilirubin, glucose, potassium and sodium, and CBC; (3) hyperprolactinaemia probably lacks of practical importance, but the further investigations are needed in this area.

[The clinical picture of acute olanzapine poisonings]. / Obraz kliniczny ostrych zatruc olanzapina.

BACKGROUND: Olanzapine is a second generation antipsychotic of thienobenzodiazepin group, which is used in the treatment of schizophrenia, bipolar disorder, and others, mainly psychiatric. Its multireceptor action (antagonism to dopaminergic D1, D2, D4, serotoninergic 5-HT2A, 5-HT2C, histaminergic H1, cholinergic M1-5, and a1--adrenergic receptors) results in multiple clinical symptoms in the course of acute poisoning. AIM OF THE STUDY: Evaluation of incidence and intensity of clinical symptoms in patients with of acute olanzapine intoxication. The pathophysiological mechanisms of particular symptoms are also described. MATERIAL: 26 patients (mean age 37.7 +/- 15.3 years) hospitalized in 2005-2008 in toxicological centers in Krakow and Gdansk because of acute olanzapine poisoning (all patients had the toxic serum level of olanzapine above 100 ng/mL). The study group consisted of 11 men (29.3 +/- 8.5 years) and 13 women (44.9 +/- 16.4 years); 1 man and 1 woman were poisoned twice. METHODS: Prospective analysis (using descriptive statistics) of data taken from medical anamnesis and results of physical examination, considering the following ones: consciousness disturbances (Glasgow Coma Scale, Matthew's scale, qualitative disturbances), vital signs (arterial blood pressure, heart rate, breathing rate, temperature), neurological findings (muscular tension, tendon reflexes, extrapyramidal symptoms, pupils) and others (oral and bronchial secretion, Poisoning Severity Score). RESULTS: The mean dose of ingested olanzapine in the study group was 352.5 +/- 220.0 mg, while the mean time since ingestion to hospital admission was 4.4 +/- 3.5 h. The half of the patients took other medicines together with olanzapine, and 23% consumed alcohol, as well. The following intensity of quantitative consciousness disturbances according to Matthew's scale were observed: grade 0 - 8%, I - 15%, II - 23%, III - 50%, and IV - 4%. The minimal and maximal values of blood pressure were: 102/63 +/- 16/14 and 163/ 97 +/- 27/18 mmHg, respectively; heart rate: 77 +/- 15 and 138 +/- 22 beats/min; temperature: 36.3 +/- 0.5 and 37.9 +/- 0.8 degrees C; breathing rate in non-intubated patients: 14 +/- 2 and 22 +/- 7 breaths/min. The mean duration of consciousness disturbances, endotracheal intubation and mechanical ventilation were: 44.9 +/- 31.3; 22.0 +/- 33.3 and 7.0 +/- 25.9 h, respectively. The study revealed tachycardia (85%), psychomotor agitation (81%), hypertension (73%), miosis (65%), and coma (54%) as the most common symptoms of poisoning. The hospitalization of poisoned patients lasted on average 5.7 +/- 3.6 days and the half of them were poisoned severely (PSS 3). CONCLUSIONS: In the course of acute olanzapine poisoning: (1) the prevailing symptoms come from circulatory and central nervous systems; (2) some symptoms are mutually opposed, eg.: coma - psychomotor agitation, hypertension - hypotension, tachycardia - bradycardia, hyperthermia - hypothermia, miosis - mydriasis; (3) rarely consciousness disturbances may persist for up to 6 days after olanzapine overdose; (4) the course of poisoning can be severe, sometimes complicated, but fatal outcomes are rare.

[Acute clozapine poisonings in years 2007 - 2010 in material of Clinic of Toxicology in Kraków]. / Ostre zatrucia klozapina w materiale Kliniki Toksykologii w Krakowie z lat 2007 - 2010.

18 patients with acute clozapine poisoning, 6 female and 12 male, were analyzed. The mean age was 42.8 years. Six patients were intoxicated only clozapine. Mixed poisoning (clozapine and other factor) was diagnosed in nine cases. Among the additional factors dominated psychotropic drugs. According to the Poisoning Severity Score (PSS) criteria in the study group was only a one mild intoxication. Acute pneumonia developed in 3 patients, acute bronchitis and rabdomyolysis were reported in one case. The most common symptoms included: agitation, confusion (83.3%), tachycardia (77.8%), CNS depression (66.7%), excessive mucus production in bronchi, hypersalivation (44.4%), miosis (50%). Disordered breathing requiring intubation or mechanical ventilation occurred in 27.7% of poisoned. The average duration of hospitalization was less than 7 days.

[Sulpiride poisoning--case report confirmed with the quantitative determination of the xenobiotic serum level]. / Zatrucie sulpirydem--opis przypadku potwierdzony ilosciowym oznaczeniem stezenia ksenobiotyku w surowicy.

Despite above 40 years the presence of sulpride on the pharmaceutical market, the acute poisonings are poorly reported in the medical literature. The discussed case of sulpiride intoxication concerns ingestion probably dose of 12 g, that exceeded 10-fold maximum therapeutic dose. 16-year-old girl, with no previous sulpiride treatment, was admitted to the Toxicology Department about 3 hours after ingestion. In clinical picture she presented quantitative consciousness disturbances with maximum 10 scores in GCS scale, with tendency to low BP (minimum 88/45 mmHg) and episode of orthostatic hypotension. The ECG demonstrated: normogram, sinus tachycardia with a heart rate of 125 beats/min, PQ = 120 ms, QRS = 80 ms, prolongation of QTc to 519,6 ms and unspecific changes of ST-T syndrome. The qualitative toxicological test confirmed the presence of chlorprothixene in urine, but the serum therapeutic concentration (0.126 microg/ml) excluded the overdose. The quantitative determination of sulpiride serum concentration confirmed acute sulpiride poisoning. The measured sulpiride toxic concentration on admission and in the consecutive hours were from 13.2 to 8.2 microg/ml. Sulpiride toxicokinetic parameters such as t max = about 3 h, t 1/2 = 24.02 h, k(el) = 0.029 h(-1) were also estimated. They point out that the absorption rate is similar and the elimination is prorogated in sulpiride acute poisoning compared to therapeutic doses.

[Amanitin determination in mushroom poisoning diagnostics]. / Oznaczanie amanityny w diagnostyce zatruc grzybami.

There are some serious poisonings with toxic mushroom species in Poland every year. Good prognostics in the cases is correlated to short time from mushroom consumption to hospitalization, correct distinguish not specific gastrointestinal and Amanita phalloides syndrome and immediately specific treatment. The purpose of the paper was to make appraisal of usefulness of amanitin blood and urine determination and transaminases activity determination (ALT, AST) in diagnostics of mushroom poisoned patients up to three days after mushroom consumption. The material was twenty two retrospective histories of mushroom poisoned patients treated in the years 2007-2008. Amanitin blood and urine determinations were made by ELISA method. Urine amanitin results in samples collected within 40 h from mushroom consuming were positive in all Amanita phalloides syndrome cases. Serum amanitin determination was not useful for the diagnostics. Trans-aminases activity determinations let to distinguish Amanita phalloides syndrome on the second and the third day after mushroom consumption. In the first poisoning phase (within 24 h), the ALT and AST activities were in normal ranges and only amanitin urine determination let to confirm or exclude Amanita phalloides poisoning. Amanitin urine determinations were useful to take fast decision about specific treatment and avoid internal organs dysfunctions.

[Toxicity of sulpiride]. / Toksycznosc sulpirydu.

Sulpiride is a benzamide neuroleptic used in the treatment of some psychiatric and gastroenterological disorders. Its antipsychotic, antiautistic, activizing and antidepressive properties result from antagonistic action to dopaminergic D2, D3 and D4 receptors in the central nervous system (CNS). The oral bioavailability of sulpiride is poor and it does not appear to have an extensive first-pass metabolism, nor is it extensively protein-bound. Elimination of sulpiride appears to depend primarily on the kidneys. The acute sulpiride poisoning includes mainly neuropsychiatric (i.e., agitation, hallucinations, and CNS depression) as well as cardiac effects (i.e., hypotension, dysrhythmias, and sinus tachycardia). The life-threatening conditions with sometimes fatal outcome after sulpiride poisoning are prolongation of QTc interval with consequent torsade de pointes (TdP) and neuroleptic malignant syndrome (NMS). The quantitative methods for the measurement of sulpiride blood concentration are not routinely available and the toxic blood concentration is probably higher than 2 mg/L. Treatment of acute sulpiride poisoning includes standard protocols of gastrointestinal decontamination and further symptomatic and supportive measures, among them TdP (magnesium sulphate, isoproterenol, electrotherapy) and NMS treatment (benzodiazepines, bromocriptine, dantrolene, physical cooling).

[The review of acute risperidone poisoning]. / Ostre zatrucie risperidonem--przeglad zagadnienia.

Risperidone (RIS) is a benzisoxazole derivative, an atypical neuroleptic used in the treatment of schizophrenia and other psychoses. The therapeutic action of RIS depends not only on the parent compound but also its major active metabolite, 9-hydroxyrisperidone (9-OH-RIS), and the pharmacokinetics is modified by the genetic polymorphism of CYP2D6, the main site o RIS metabolism. Diverse symptoms of an acute RIS poisoning result from its interaction with multiple receptors, i.e. serotoninergic 5-HT2A and 5-HT7, dopaminergic D2, adrenergic alpha1 and alpha2, as well as histamine H1. The clinical picture of acute RIS poisoning consists predominantly of central nervous system and cardiovascular effects and the most severe symptoms are: hypotension, dysrrhythmias, consciousness disturbances, seizures and respiratory failure. No specific antidote for RIS poisoning is known and the treatment is only symptomatic and supportive. Quantitative determination of RIS blood concentration seems to be helpful in confirmation and monitoring of acute poisoning, nevertheless further investigations are needed to evaluate the relation between drug concentration and clinical symptoms.

[Development of analytical method for determination nicotine metabolites in urine]. / Opracowanie metody oznaczanie metabolitów nikotyny w moczu.

The assay of biomarkers in biological material is the most popular and reliable method in estimate exposure to tobacco smoke. Nicotine and its metabolites qualify to the most specific biomarkers for tobacco smoke. Currently the most often used are cotinine and trans-3'-hydroxycotinine. The aim of this study was development of easy and quick method of determining nicotine and its main metabolites with high performance liquid chromatography--available in most laboratories. Nicotine and its metabolites in urine (cotinine, trans-3'-hydroxycotinine, nornicotine and nicotine N-oxide) was determined by means of high performance liquid chromatography with spectrometry detection (HPLC-UV). The determined compounds were extracted from urine by means of the liquid-liquid technique, before analysed by the HPLC method. Developed technique of high performance liquid chromatography proved to be useful to assessment nicotine and its four metabolites in smokers, though further research are necessary. The further modification of procedure is required, because of the interferences of cotinine N-oxide with matrix, which prevent determination. Increasing the efficiency of extraction nicotine and nornicotine could enable the determination in people exposed on environmental tobacco smoke (ETS). This study confirm other authors' observations that 3'-hydroxycotinine might be equivalent with cotinine predictor of tobacco smoke exposure, however further studies are required.

[Tobacco smoking by alcohol addicted patients--preliminary report]. / Palenie tytoniu przez pacjentów leczonych z powodu uzaleznienia od alkoholu--doniesienie wstepne.

The problem of alcohol and nicotine addiction is both social and medical. The substances are often used together and give complex addiction. The knowledge about mechanisms of complex addiction would be useful for creating effective ways of treatment the abused patients. The aim of the paper was to describe the complex ethanol and nicotine addiction phenomenon. The research was made using data from 30 ethanol and nicotine addicted patients treated in Clinic of Toxicology Jagiellonian University Collegium Medicum in Krakow. 90% of them were nicotine addicted. Tobacco was the first abused substance in the group of patients. The mean period of addiction was 29.0 years for tobacco and 22.2 years for alcohol. The majority of the patients (51.9%) smoked more than 20 cigarettes per day; 29.6% smoked 11-20 cigarettes per day. Single patients were narcotics and drugs addicted. Continuation of the research and toxicological determination of the substances and their metabolites concentrations would be useful for the complex addiction problem explanation and description.

[Extended suicidal poisoning with carbamazepine and phenothiazine derivatives]. / Rozszerzone samobójcze zatrucie karbamazepina i fenotiazynami.

UNLABELLED: Two cases (woman and man) of the extended suicidal poisonings with carbamazepine and phenothiazine derivatives are presented. Drug's blood concentrations during poisoning were monitored. We examine correlation between patient's general status and the drug's blood concentrations, carbamazepine and phenothiazine derivatives interaction due to young, healthy people who received no earlier treatment. MATERIAL AND METHODS: blood samples for toxicological examinations were collected at 0, 12, 24 and 48 hours after admission. Carbamazepine was determined using FPIA method and phenothiazines derivatives by HPLC-DAD. The highest blood concentrations were for carbamazepine: 30.92 mg/l (woman) and 20.95 ng/ml (man); for phenothiazine derivatives: 927 ng/ml (woman) and 733 ng/ ml (man). CONCLUSIONS: In both cases severe central nervous depression was observed due to summed action of the drugs. Sex and individual differences in cytochromes activities should have influence to carbamazepine metabolism and faster elimination time in woman. In the case of phenothiazine derivatives faster elimination time in man was observed. The differences in elimination times between compared drugs confirm their different metabolic routes.

Disposition of valproic acid in self-poisoned adults.

Acute intoxication with valproic acid is increasingly being observed in clinical practice. In Poland, such intoxication frequently occurs as a result of mixing different drugs or alcohol. We studied the pharmacokinetics of valproic acid in five intoxicated patients. Apart from valproic acid, barbiturates, chlorprotixene, tricyclic antidepressants, tetrahydrocannabinols and alcohol were detected and measured. The absorption of the drug was rapid and the maximum concentration was observed after the period of 3.5-5.6 hr. The lowering of the valproic acid level in plasma was biphasic, with terminal half-life ranging between 8.8-30.9 hr. The calculated apparent volume of distribution was 0.17-0.72 l/kg and could be affected by varied levels of doses as well as time of drug intake (data from interviews of patients) used for calculation and reduction in plasma protein binding at higher concentration of valproic acid. Frequent multiple drug poisonings oblige toxicological laboratories not only to monitor valproic acid concentration in serum, but also to perform the toxicological screenings.

Monitoring of verapamil enantiomers concentration in overdose.

A 52-year-old woman with a history of depression and personality disorders, hypertension, coronary disease and asthma was admitted to the Department of Clinical Toxicology after taking 60 tablets of Staveran (immediate release verapamil), and 4 tablets of acetaminophen. One and a half hours after ingestion her condition was critical. She required endotracheal intubation and artificial respiration. Her heart rate was 75 beats per minute, (bpm) and her blood pressure dropped from 70/50 to 50/00 mmHg. Additionally, drowsiness and headache were observed. On admission, R-(+)- and S-(-)-verapamil serum concentrations were 2252 ng/ml and 810 ng/ ml, respectively. Monitoring of the verapamil serum concentration was carried out over 74 h. Terminal elimination half-lives were 18.7 (21.3) and 17.0 (18.5) hours, respectively, for R-(+)- and S-(-)-verapamil. Monitoring of verapamil enantiomers concentrations in serum indicated a higher concentration of the less active form and slightly faster elimination of the more active enantiomer. The data-support a stereoselective difference between first pass clearance and later systemic clearance of verapamil, when taken in overdose.

B-type natriuretic peptide plasma concentration in acutely poisoned patients.

B-type natriuretic peptide (BNP) is synthesized in the cardiac ventricles upon ventricular myocyte stretch. BNP plasma concentration is useful in cardiology especially for identifying patients with congestive heart failure (CHF), as a prognostic marker of acute coronary syndromes and independent predictor of sudden cardiac death. Its value in clinical toxicology is unclear. As toxins frequently produce deleterious effects on the cardiovascular system we have decided to carry out the pilot study on BNP plasma levels in acutely poisoned patients. The 117 patients (65 males and 52 females) treated at the Department of Clinical Toxicology Jagiellonian University Medical College in Kraków in 2004 were included. 42 of them were intoxicated with ethanol, 35 with pharmaceuticals (mostly tricyclic antidepressants), 13 with CO. The mean age of examined group was 34.07 +/- 12.08 year. The control group consisted of 54 healthy volunteers and employees of the Department (mean age; 32.7 +/- 11.74). A significantly higher BNP concentration was found in poisoned patients than in the control group. The highest BNP plasma concentration was noted in pharmaceutical poisoned patients. Mean BNP concentration in poisonings of minor severity (grade 1) was significantly lower then in moderate (grade 2) or severe (grade 3) poisonings. BNP plasma measurement as an additional marker of cardiac disturbances in clinical toxicology practice may be suggested.

Comparison of fluorescence polarization immunoassay and high performance liquid chromatography for determination of carbamazepine concentration in blood of poisoned patients.

Carbamazepine is an antiepileptic drug widely used by neurological and psychiatric patients. Because of it's low therapeutic index and increasing number of acute carbamazepine intoxications there is a need of routine serum carbamazepine assay in toxicological laboratories. Determinations of serum carbamazepine concentrations are 5.3% of all toxicological analysis carried on in Department of Analytical Toxicology and Therapeutic Drug Monitoring, Collegium Medicum, Jagiellonian University in Kraków. The goal of the study was comparison of two analysis methods: FPIA and HPLC-DAD for the diagnostics of patients intoxicated with carbamazepine. Material for analysis were 21 samples of blood collected from poisoned patients treated in Department of Clinical Toxicology in Kraków. Measurements of serum carbamazepine concentration by FPIA method and carbamazepine and it's main active metabolite carbamazepine-10,11-epoxide concentrations by HPLC-DAD method were made. Statistical analysis showed that serum carbamazepine concentrations measured by FPIA method were higher than serum carbamazepine concentrations measured by HPLC-DAD method (t21 = 2.21, p = 0.0384). The mean difference of serum carbamazepine concentrations measured by the two methods was 2.67 mg/l (SD = 5.69 mg/l) and didn't depend on the carbamazepine concentration measured by FPIA method (r = -0.137, p = 0.5431). There was no statistical difference between serum carbamazepine concentration measured by FPIA method and the sum of serum carbamazepine and carbamazepine-10,11-epoxide concentrations measured by HPLC-DAD method (t21 = 1.42, p = 0.1690).

[Psychoactive substances in biological samples--toxicological laboratory data]. / Substancje psychoaktywne w materiale biologicznym--dane z laboratorium toksykologicznego.

The subject of the research was the analysis of frequency and type of psychoactive substances used, basing on the determinations the blood and/or urine samples, performed in the toxicological laboratory of the Department of Clinical and Industrial Toxicology Jagiellonian University in Kraków in the period from December 2001 to November 2003. From 17,649 performed determinations--45.5% were positive. 50% of the positive determinations were psychoactive substances. The most often psychoactive substance determined was ethyl alcohol (52.86%), next benzodiazepines (17.41%), amphetamines (10.54%), opiates (8.05%), THC (6.87%), barbiturates (3.74%), and occasionally atropine and cocaine. There was observed a variety of mixed, simultaneously taking psychoactive substances, especially ethyl alcohol, opiates, amphetamine derivatives and cannabinoids. The analysis of the occurrence of psychoactive substances in biological samples from patients treated in different hospital departments, others hospitals and ordered by private persons also was performed. In the last two years 369 private patients ordered psychoactive substances determinations and 78 of them were positive.

[Proper use of own data bases warranted by call recording system]. / System rejestracji rozmów warunkiem wlasciwego wykorzystania wlasnych baz danych.

A newly created computer system for call (toxicological information) recording and a Base of Toxic Substances created in native Polish language are presented in the paper. An extended structure of this data base enable to catalogue different groups of toxic substances (e.g. medication drugs, psychoactive substances, pesticides), and toxins (animals' poisons, toxic plants and mushrooms) concerning their specificity. Construction of the Base also enable to reach necessary information quickly. What more, identification of toxic substances could be easier due to possibility enclosing photos.

[The effect of smoking on serum nitric oxide (NO) in acutely carbon monoxide poisoned patients]. / Wplyw palenia tytoniu na stezenie tlenku azotu w surowicy krwi pacjentów ostro zatrutych tlenkiem wegla.

An important role of Nitric Oxide (NO) in relaxing vascular smooth muscle is commonly known. In this pilot study we aimed to asses an impact of cigarette smoking on NO serum concentration in acutely CO poisoned patients. The measured marker of cigarette smoking was urea cotinine. A highest NO concentration and lowest diastolic blood pressure were noted in the subgroup of acutely CO poisoned smokers. Diastolic blood pressure in the subgroup of not CO poisoned non-smokers and was higher compared to acutely CO poisoned (both smokers and nonsmokers) and also to subgroup of those person who were exposed only to CO in cigarette smoke.

[The level of cotinine in urine and placenta of women smoking or exposure to tobacco smoke during pregnancy]. / Poziom kotyniny w moczu i lozysku kobiet palacych tyton i narazonych na ETS w czasie ciazy.

The aim of the studies was evaluation smoking habit by delivering woman using objective method--determination of cotinine in urine and placenta. In the study participated 93 woman delivering in Gynaecological-Obstetric Clinical Hospital of Medical University at Warsaw. Evaluation of tobacco smoking and exposure to ETS performed on the base of questionnaire and level of cotinine in urine. In the group of non smoking woman cotinine was not detected any in urine any in placenta. In the second group (19 patients), woman exposure to ETS concentration of cotinine in urine was 28.9 +/- 14.9 ng/mg of creatinine and only in two placentas was detected a low level of cotinine. In smoking delivering woman the urine concentration was 837.0 +/- 1324.5 ng/mg of creatinine and 21.3 +/- 7.5 ng/g placenta calculated from all results and 67.0 +/- 3.5 ng/g calculated only from positive results. A weak relation between concentration of cotinine in placenta and urine of smoking woman was shown.