[Pharmacokinetic implication of an acute meprobamate poisoning case].
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Biomedical subjects
Publications and source records attributed to I Ijiri.
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A method for electrochemical determination of p-hydroxymethamphetamine and p-hydroxyamphetamine in human urine was investigated by column liquid chromatography. A rapid and simple extraction of these substances from urine was performed using a solid-phase extraction column. The detection limit for quantitation was approximately 50 pg for the metabolites. The simplicity and sensitivity of this method allows for analysis of these metabolites in the fields of toxicology and forensic medicine.
p-Hydroxymethamphetamine and p-hydroxyamphetamine in urine samples from methamphetamine addicts were analyzed by high-performance liquid chromatography-electrochemistry (HPLC-EC). The urine samples were hydrolyzed with equal volumes of 12 N HCl at 60 degrees C for 4 h and were then diluted with water and neutralized with NaOH solution. The neutralized urine was passed through a solid phase extraction column, Bond-Elut C18, and after washing, the substances were eluted with acidified acetonitrile. The eluate was evaporated under a stream of nitrogen. The residue was dissolved in 0.1 N PCA and a small volume of the aliquots was injected into the HPLC. This procedure for determination quantitated both free and conjugated forms of the metabolites together. Thereby we could determine concentrations of the metabolites in minute urine samples; i.e., from 2.5 microliters urine. The free form of the metabolites alone was analyzed by the same procedure except for hydrolysis of the conjugates. Concentrations of methamphetamine, p-hydroxymethamphetamine and p-hydroxyamphetamine in the urine samples of addicts collected at arbitrary times were determined by this procedure or by gas chromatography. It was found that there was no correlation between the concentration of methamphetamine and that of the metabolites. This investigation also revealed that various ratios between the concentrations generally were scattered over a wide range of percentages.
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The effect of heating on Y-chromosome detection was investigated. Heat-treated blood was divided into four groups according to the hemolysis pattern obtained by the coil planet centrifuge system. A significant difference between the Y-positive nuclei of males and females was observed up to group III of the hemolysis pattern, and it was possible to determine the sex of the blood donor in spite of karyolysis and degeneration of blood components. However, sex determination of blood in group IV, indicating complete hemolysis, was impossible because of overlapping between male and female Y-chromosome counts. Practical application of this sex determination method was successful even with severely burned cadavers. However, it was suggested that putrefaction together with heat damage made the identification nearly impossible.
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Normal Japanese subjects were divided into two groups, i.e., one with both low and high Km isozymes of aldehyde dehydrogenase for acetaldehyde, and the other deficient in the low Km isozyme. After intake of 0.4 g/kg alcohol, the deficient subjects showed high level of blood acetaldehyde, facial flushing and the other dysphoric symptoms, including increase of pulse rate, decrease of diastolic blood pressure, changes of pulse wave in the fingertip, and elevation of the arterial pressure and blood flow rate in common carotid arteries as well as increase of plasma catecholamines level. In contrast, subjects with normal ALDH did not show these changes. From the observation of liver specimens obtained at autopsy, the frequency of deficient phenotype of ALDH in Japanese was presumed to be about 36%.
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Sixty three male Japanese, aged 20-40 yr were evaluated as to the degree of facial flushing following a controlled dose of ethanol either as Japanese rice wine or ethanol 0.4 g kg body weight. Thirty four subjects responded with overt facial flushing. The acetaldehyde levels in blood and expired air were significantly higher in the flushing group without a change in ethanol elimination rate. Urinary excretion of Vanilmandelic acid (VMA) and 3 methyoxy-4-Hydroxyphenylglycol (MHPG) are reported.
Normal subjects were divided into two groups, i.e., those showing, and those not showing, facial flushing after consuming a small amount of alcohol. In the flushing group, increases of pulse rate, facial skin temperature and carotid arterial pressure and blood flow rate, as well as changes of digital plethysmogram and electrocardiogram, were found together with a conspicuous rise in blood acetaldehyde levels after the drinking. However, significant changes of the signs as mentioned above and elevation of blood acetaldehyde did not occur in the non-flushing group. The maximum blood alcohol levels and the rate of alcohol elimination showed not difference between these two groups. Furthermore, urinary excretions of epinephrine and norepinephrine increased in the flushing cases after the drinking.
Positional nystagmus and body sway were measured for 8 hours following alcohol ingestion in 27 human volunteers. The intensity of positional alcohol nystagmus phase I (PAN-I) correlated well with blood alcohol concentration (BAC) along the time axis; the correlation coefficient between PAN-I and BAC 1 hour after alcohol ingestion was 0.62 (P less than .01). The minimum threshold BAC resulting in PAN-I was 0.23 mg/mL. Body sway was measured by stabilometry. The circumscribed area of posturography before and after alcohol ingestion was compared. Temporal changes in body sway and BAC were also closely correlated. The BAC threshold for increased body sway was estimated to be somewhere between 0.5 and 0.8 mg/mL, considerably higher than the threshold for PAN-I. Measurements of blood acetaldehyde, the dehydrated product of ethanol metabolism, showed no correlation with either the intensity of PAN or changes in body sway. The intensity of PAN and body sway measured at the time of peak BAC 1 hour after alcohol ingestion, however, showed significant positive correlation (r = .50, n = 25; P less than .01).
The regulation mechanism of inhibition of intestinal ethanol absorption induced by high acetaldehyde (AcH) concentration in blood was investigated. We used atropine (AT), atropine methylbromide (ATMB), pirenzepine (PI), bethanechol (BE) and pilocarpine (PL) with or without cyanamide (CY; a potent inhibitor of aldehyde dehydrogenase, which induces high AcH concentration in blood). The K(a) (absorption rate constant) value after the CY-alone pretreatment was significantly lower than that in controls. In the high AcH-induced cases, the values of K(a) in AT and ATMB pretreatments were similar to controls, but the value of K(a) in PI pretreatment was lower than that in controls. The values of K(a) in the case of BE pretreatment with and without high AcH levels were lower than in controls. The K(a) value in the PL with CY was significantly lower than that with CY alone. However, its action was blocked by ATMB pretreatment. These results suggest that high blood AcH concentrations inhibit intestinal ethanol absorption through the peripheral cholinergic nerves via muscarinic receptors, except for the muscarinic M(1) receptor, compared to other subtypes of muscarinic receptors.
A simple, sensitive, and rapid quantitative method for Dipterex in serum is described. A SepPak C18 cartridge for the extraction and gas chromatography with flame thermionic detection for determination are used. The detection limit is 2.5 ng/mL, and linearity is obtained in the range 5-500 ng/mL.
We report a simple, sensitive, and rapid quantitation of Amitraz in plasma after Extrelut-3 column extraction by gas chromatography with nitrogen-phosphorus detection (GC-NPD). The plasma sample was diluted four-fold with borate buffer (0.01M, pH 11), put into an Extrelut-3 column, left for 15 min, and then eluted with 15 mL of n-hexane. The n-hexane eluate was evaporated under nitrogen gas flow at room temperature. The residue was reconstituted with 0.1 mL of acetone containing nitrazepam as an internal standard. A 2-microL aliquot was injected into a wide-bore capillary column GC-NPD. The detection limit was 0.5 ng/mL and linearity was obtained in the range of 1-200 ng/mL. Amitraz in the buffer at pH 11 remained stable in a freezer for one week at -20 degrees C. The GC-NPD method was found useful in studying the pharmacokinetics of a single dose intravenous administration of Amitraz to a dog.