Pharmacokinetics of tiapride in patients with tardive dyskinesia and Huntington's disease.

The pharmacokinetics of tiapride were determined at steady-state in 5 patients with tardive dyskinesia and 2 patients with Huntington's disease given tiapride 100 mg t.i.d. for 7 days. The maximum serum concentration of tiapride of 1.47 +/- 0.35 micrograms/ml was reached after 1.4 +/- 0.67 h. The half-life time of elimination was 229 +/- 41 min. About 50% of the dose of tiapride was excreted unchanged by the kidney. Neither protein binding nor glucuronide, sulphate or acetyl conjugation was observed. Renal clearance in the patients appeared to be lower but the other pharmacokinetic parameters did not differ from previous findings in healthy young volunteers.

Monitoring of aluminum in whole blood, plasma, serum, and water by a single procedure using flameless atomic absorption spectrophotometry.

A simple, time-saving procedure to measure aluminum (AI) in whole blood, plasma, and water samples of low ionic strength by flameless atomic absorption spectrometry is presented. With this procedure, an analagous pretreatment is given to all samples. Moreover, the pretreated samples are analyzed using an identical program of the atomic absorption spectrophotometer. The detection limit is 1.3 micrograms/L for aqueous solutions and 1.9 micrograms/L, 1.8 micrograms/L, and 2.3 microL for serum, plasma, and blood samples respectively. The precision of the method varies between 2.8% and 4.2% of all analyses. Using this method, a comparison was made between Al levels in whole blood (AlB) and plasma (AlP) in rats and AlB and AlP in renal patients. The AlB and AlP were strongly correlated. It is concluded that the monitoring of AlB may have a similar prognostic value for toxicity as the monitoring of AlP, but more experimental advantages.

Determination by flameless atomic absorption of aluminium in serum and hair for toxicological monitoring of patients on chronic intermittent haemodialysis.

Determination of aluminium in serum of patients on chronic intermittent haemodialysis is of paramount importance in the prevention or early diagnosis of aluminium intoxication. We present a new method based on flameless atomic absorption spectroscopy, in which the serum matrix is destroyed by oxygen. A comparison has been made between the described method and another procedure which is used in the Laboratory of Toxicology in Ghent, with favourable results. In addition, a method is presented for the determination of aluminium in hair, in which special attention has been paid to the cleaning of the hair samples prior to destruction. As yet it cannot be concluded whether aluminium concentrations in hair give a better representation of the body burden than serum levels do.

Experience with a screening method for laxative abuse.

1 Abuse of laxatives may lead to a variety of serious disorders which are usually difficult to recognize because of the heterogenicity of the toxic effects. 2 In order to facilitate the diagnosis of chronic laxative poisoning, a laboratory screening method for the detection of colonic stimulants in urine has been designed and has been applied in practice over a three-year-period. 3 During this period, 157 samples from 81 patients were sent to the laboratory. Fifteen patients (18.5%) were definitely shown to use self-prescribed laxatives. 4 Next to the diphenolic compounds: bisacodyl, phenolphthalein and bisoxatin, the anthraquinone derivative rhein, a metabolite of vegetable laxatives, was found in several cases. In the urine of three patients a substance resembling rhein was found, which was shown to be aloe-emodin. 5 It is concluded that chronic self-poisoning with laxatives is a fairly common disorder than can easily be overlooked. Laboratory screening of the urine of suspected patients is an economic and reliable method for its diagnosis.

Liquid-chromatographic determination of amitryptyline and its metabolites in serum, with adsorption onto glass minimized.

To study correlations between the concentrations, in serum, of amitriptyline and its most important metabolites with clinical response in patients, we developed a "high-performance" liquid-chromatographic method for routine determination of amitriptyline, nortriptyline, total 10-hydroxy-amitriptyline, desmethylnortriptyline, and E(trans)- and Z(cis)-10-hydroxynortriptyline. These compounds are extracted from 1 mL of alkalinized serum into hexane/isoamyl alcohol (99/1 by vol). Perazine is the internal standard. To minimize irreversible adsorption of the drugs onto the glassware, 5 micrograms of maprotiline is added to the organic phase just before evaporation. After a 10-min resolution on a silica column eluted with acetonitrile/methanol/NH4OH (1 mol/L), absorbance is measured at 240 nm. Only chlorimipramine, doxepin, procainamide, and N-acetylprocainamide may interfere with assay of the compounds that probably are therapeutically relevant: amitriptyline, nortriptyline, and E-10-hydroxynortriptyline. Uremia, lipemia, and icterus also do not affect the analysis.

A screening method for establishing laxative abuse.

Abuse of laxatives, most of them belonging to the group of colonic stimulants or cathartics, can cause various disorders. Extensive diagnostic work can be avoided by early toxicological screening of the suspected patients with respect to laxatives. Because no screening method of this kind was available, we developed a procedure with which all phenolic and anthraquinone laxatives--except sodium picosulfate--can be detected in urine. This method is based on high-performance thin-layer chromatography in two systems after pretreatment of a 20-mL urine sample with beta-glucuronidase and subsequent column extraction. The procedure is very sensitive: at least 32 h after a single dose of bisacodyl, danthron, phenolphthalein, or sennoside, the drug can be detected in the urine. Bisoxatin and oxyphenisatin are still detectable in the urine 18 h after intake. The method is also highly specific; none of 73 other drugs interfered in either of the two chromatographic systems. This procedure can be helpful for the early diagnosis of laxative abuse.