Colchicine poisoning: report of a fatal case with body fluid analysis by GC/MS and histopathologic examination of postmortem tissues.

A suicide caused by oral ingestion of colchicine is reported. Postmortem examination revealed circulating Pelger-Huet polymorphonuclear leukocytes and numerous mitotic and chromatin bodies in tissues with rapid cell turnover. Colchicine was identified by gas chromatography/mass spectrometry (GC/MS) of an organic extract of a urine specimen obtained about 36 h after the patient's original hospitalization. The clinical history and pathology of this rarely encountered intoxication are correlated with previous reports, and the rapid detection of colchicine by GC/MS is discussed.

Simultaneous high-performance liquid chromatographic analysis of carbidopa, levodopa and 3-O-methyldopa in plasma and carbidopa, levodopa and dopamine in urine using electrochemical detection.

Two assay procedures are described for the analysis of levodopa, carbidopa and 3-O-methyldopa in plasma and levodopa, carbidopa and dopamine in urine. The methods are suitable for quantifying the analytes following therapeutic administration of levodopa and carbidopa. Both were based on reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection and with methyldopa as the internal standard. Plasma samples were prepared by perchloric acid precipitation followed by the direct injection of the supernatant. Urine was prepared by alumina adsorption, and the analytes were desorbed with perchloric acid solution containing disodium EDTA and sodium metabisulfite prior to injection into the HPLC system. The methods have been utilized to evaluate the pharmacokinetics and bioavailability of oral dosage forms containing levodopa and carbidopa.

Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies.

The pharmacokinetics of Sinemet CR, a controlled-release formulation containing carbidopa and levodopa, were investigated in healthy young and elderly volunteers and in patients with Parkinson's disease. Sinemet CR produced more sustained plasma levels of levodopa, carbidopa, and 3-O methyldopa than did conventional Sinemet. In elderly subjects, the corresponding steady-state plasma levels fluctuated in narrower ranges with Sinemet CR than those following the administration of Sinemet. Results indicate a levodopa bioavailability of 71% for Sinemet CR, in contrast to a bioavailability of 99% for Sinemet for these subjects. The carbidopa bioavailability of Sinemet CR was 58% relative to that of Sinemet. Systemic decarboxylase inhibition was comparable between the 2 regimens as indicated by the renal clearance of levodopa. The absorption of levodopa was slower and more protracted with Sinemet CR than with Sinemet. Food increased the levodopa bioavailability of Sinemet CR. This increase was attributed to an increased gastric retention time. No dose-dumping occurred with Sinemet CR in either the nonfasting or the fasting state. Levodopa bioavailability was lower in young volunteers than in elderly volunteers. This was attributed to an age-related decrease in gastric emptying and in 1st-pass metabolic decarboxylation in the gastrointestinal (GI) tract. In parkinsonian patients, as in healthy subjects, the Sinemet CR formulation produced more sustained levodopa plasma levels. These patients required a higher total daily dosage of Sinemet CR than of Sinemet for control of parkinsonian symptoms, but less frequent dosing was required during chronic therapy. Peak plasma levodopa levels increased proportionately with increasing Sinemet CR dosage. These observations were consistent with the pharmacokinetic characteristics of the formulation.

Bioanalysis and disposition of alpha-fluoromethylhistidine, a new histidine decarboxylase inhibitor.

A sensitive, selective, and rapid high-performance liquid chromatographic procedure was developed for the determination of alpha-fluoromethylhistidine (alpha-FMH) in human biological samples. The plasma assay required isolation of the drug using a weak cation-exchange resin prior to HPLC analysis with UV detection. The urine assay employed postcolumn derivatization with o-phthalaldehyde (without a thiol) and fluorescence detection. The extent of metabolism of alpha-FMH in humans was studied in four healthy volunteers using tritium-labeled material. No significant differences in the plasma and urine concentrations of radioactivity and unchanged drug were detected. In addition, the radiochromatograms of selected urine samples revealed a single peak with a retention time corresponding to the unchanged drug. The evidence presented suggests negligible biotransformation of alpha-FMH in humans.