Oxidative phenotype polymorphism (P450 2D6) and metabolism of toluene.

Oxidative phenotype P-450 2D6 was examined using sparteine test in 3 groups of persons to determine if there is a coincidence in the defect of the oxidative biotransformation of sparteine and impaired oxidation of toluene, which could explain interindividual differences in the amounts of hippuric acid in the urine in exposed persons. The following groups of persons were examined: 30 rotogravure printers exposed to toluene vapors at concentrations of 8-307 ppm; 20 workers, 2 months after the cessation of the long-term exposure to toluene at concentrations of 104-1,170 ppm; 48 healthy volunteers with no exposure to toluene. Among the 98 persons 5 poor metabolizers (PMs) of sparteine were found, none in the group of printers exposed to toluene. In the experimental exposure chamber 5 PMs and 6 extensive metabolizers (EMs) were exposed to toluene concentration of 245 ppm for 5 hours. Hippuric acid and o-cresol in the urine, and toluene both in blood and in alveolar air were measured. However, no significant differences were found in either of these parameters between the PM and EM groups. Thus, the sparteine test does not appear to be applicable in the identification of persons with higher risk arising from toluene exposure.

Phenytoin as a risk factor in gingival hyperplasia.

Fifty-four out-patients with epilepsy who had been taking phenytoin for more than one year were examined for gingival hyperplasia. Approximately 76% of patients showed either mild or no gingival hyperplasia. Lesion severity was then compared statistically to phenytoin dosage and drug concentrations as well as to other clinical and laboratory parameters. There was a tendency for gingival hypertrophy to be associated with both increasing dosage of phenytoin per unit of body weight and the duration of phenytoin administration. All patients followed had a statistically significant progressive trend to increasing gingival hyperplasia with higher total and free phenytoin concentration.

Pharmacokinetics of ethyl biscoumacetate and its metabolite 7-hydroxy ethyl biscoumacetate in healthy volunteers.

Disposition kinetics of ethyl biscoumacetate and its metabolite 7-hydroxy ethyl biscoumacetate were evaluated in ten healthy volunteers, after a single 300 mg oral dose of ethyl biscoumacetate. Serum concentrations of parent compound and its metabolite were measured by HPLC. The maximum serum ethyl biscoumacetate concentrations were reached 1.0-4.0 hours after drug dosing. From 3 hours after drug administration the concentration of the metabolite was always higher than the concentration of the parent compound. Geometric mean of elimination half-life was 0.66 hours for ethyl biscoumacetate and 2.03 hours for the 7-hydroxy ethyl metabolite.

[Determination of caffeine using high-performance liquid chromatography]. / Stanovení kofeinu metodou vysokoúcinné kapalinové chromatografie.

The present paper reports a method of caffeine assay in human saliva using high-performance liquid chromatography (HPLC). Samples of saliva were extracted into a mixture of chloroformisopropanol, the extract was evaporated at 40 degrees C and reconstituted with 100 microliters of methanol. The internal standard was 8-chlorotheophylline, the mobile phase consisted of 30 parts of methanol and 70 parts of 0.01 KH2PO4 buffer, the acidity of which was adjusted to pH = 4 conc.H3PO4. The column NUCLEOSIL C18 5 microns, 250 x 4 mm, was employ for separation, UV detection, 254 nm. The chromatograms are shown in Fig. 1. The introduced method was verified when determining caffeine concentrations in patients with liver cirrhosis and in control persons. The results are shown in Table 2. The calibration curve is linear in the range of the concentrations determined from 0.5 to 10 mg/l with the regression coefficient r1,2 = 0.990. Good reproducibility of the method is characterized by the low values of the relative standard deviations (Table 1). The reported manner of caffeine determination in saliva can be utilized to evaluate liver metabolic capacities.

Determination of ethyl biscoumacetate and its metabolite 7-hydroxyethyl biscoumacetate in human serum by high-performance liquid chromatography and mass spectrometry.

An efficient reversed-phase high-performance liquid chromatographic method has been developed for the determination of ethyl biscoumacetate (EBA) and its metabolite in human serum, using the mu Bondapak C18 column and methanol-water-phosphoric acid (56:46.8:0.2, v/v/v) as the mobile phase. This method permitted the determination of both EBA and a metabolite in human serum. The latter has been mentioned by other authors only in urine samples, where significant concentrations were found. Identification of the metabolite as 7-hydroxyethyl biscoumacetate was based on its chromatographic separation, followed by isolation from the eluate and direct mass spectrometric identification. It has been found that the higher EBA concentrations in human serum described by Brodie et al. [J. Pharmacol. Exp. Ther., 106 (1952) 453] were caused by the insufficient resolving power of the spectrophotometric method used, leading to overlapping of the UV spectra of the parent drug and its metabolite.