The kinetics of alpha and beta amanitin were studied in 45 patients intoxicated with Amanita Phalloides. The amatoxins were analyzed by high performance liquid chromatography in plasma (43 cases), urine (35 cases), gastroduodenal fluid (12 cases), feces (12 cases) and tissues (4 cases). All patients had gastrointestinal symptoms and 43 developed an acute hepatitis. Two patients underwent successful liver transplantation. Eight patients, of whom three were children, died. The detection of amatoxins in the biological fluids was time dependent. The first sample was obtained at an average of 37.9 h post ingestion in the patients with positive results and at 70.6 h in the samples without detectable amatoxins. Plasma amatoxins were detected in 11 cases at 8 to 190 ng/mL for alpha and between 23.5 to 162 ng/mL for beta. In 23 cases amatoxins were detected in urine with a mean excretion per hour of 32.18 micrograms for alpha and 80.15 micrograms for beta. In 10 patients the total amounts eliminated in the feces (time variable) ranged between 8.4 and 152 micrograms for alpha amanitin and between 4.2 and 6270 micrograms for beta amanitin. In three of four cases amatoxins were still present in the liver and the kidney after day 5. Amatoxins were usually detectable in plasma before 36 h but were present in the urine until day 4. The rapid clearance indicates that enhanced elimination of amatoxins requires early treatment. Clearance of circulating amatoxins by day 4 spares the transplanted liver.

Lithium kinetics were studied in 14 patients with lithium poisoning. Three patients were treated by hemodialysis. Serum lithium peak concentrations ranged between 1.4 and 9.6 mmol/L. The apparent mean serum half-life was 23.16 +/- 9 h, the mean total clearance was 26.5 +/- 13.3 mL/min and the mean renal clearance was 17.2 +/- 5.4 mL/min. The kinetic parameters were dependent on the duration of the study and on the type of the poisoning: acute, acute upon chronic or chronic. During the first 12 h after admission ten patients were in a distribution phase, three were in an elimination phase and one was in an absorption phase. The serum half-life during hemodialysis ranged from 3.6 to 5.7 h and hemodialysis clearance was 63.2 to 114.4 mL/min. The mean volume of distribution calculated in six cases was 0.63 +/- 0.09 L/kg. The evolution of the lithium pools showed a different kinetic pattern between the extra- and the intracellular pool which decreased more slowly. During hemodialysis the decrease of the extracellular pool was about twice that of the cellular pool. Among the factors which may modify lithium toxicity and kinetics, are the type of the poisoning, the presence of an underlying disease and renal impairment. No general and rigid indication for hemodialysis can be set, but the need for hemodialysis should be based on clinical and kinetic data determined during the 12 h following admission.

The toxicities of antimalarial drugs vary because of the differences in the chemical structures of these compounds. Quinine, the oldest antimalarial, has been used for 300 years. Of the 200 to 300 compounds synthesised since the first synthetic antimalarial, primaquine in 1926, 15 to 20 are currently used for malaria treatment, most of which are quinoline derivatives. Quinoline derivatives, particularly quinine and chloroquine, are highly toxic in overdose. The toxic effects are related to their quinidine-like actions on the heart and include circulatory arrest, cardiogenic shock, conduction disturbances and ventricular arrhythmias. Additional clinical features are obnubilation, coma, convulsions, respiratory depression. Blindness is a frequent complication in quinine overdose. Hypokalaemia is consistently present, although apparently self-correcting, in severe chloroquine poisoning and is a good index of severity. Recent toxicokinetic studies of quinine and chloroquine showed good correlations between dose ingested, serum concentrations and clinical features, and confirmed the inefficacy of haemodialysis, haemoperfusion and peritoneal dialysis for enhancing drug removal. The other quinoline derivatives appear to be less toxic. Amodiaquine may induce side effects such as gastrointestinal symptoms, agranulocytosis and hepatitis. The main feature of primaquine overdose is methaemoglobinaemia. No cases of mefloquine and piperaquine overdose have been reported. Overdose with quinacrine, an acridine derivative, may result in nausea, vomiting, confusion, convulsion and acute psychosis. The dehydrofolate reductase inhibitors used in malaria treatment are sulfadoxine, dapsone, proguanil (chloroguanide), trimethoprim and pyrimethamine. Most of these drugs are given in combination. Proguanil is one of the safest antimalarials. Convulsion, coma and blindness have been reported in pyrimethamine overdose. Sulfadoxine can induce Lyell and Stevens-Johnson syndromes. The main feature of dapsone poisoning is severe methaemoglobinaemia which is related to dapsone and to its metabolites. Recent toxicokinetic studies confirmed the efficacy of oral activated charcoal, haemodialysis and haemoperfusion in enhancing removal of dapsone and its metabolites. No overdose has been reported with artemesinine, a new antimalarial tested in the People's Republic of China. The general management of antimalarial overdose include gastric lavage and symptomatic treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

1 A 21 year-old student ingested thirty ricin seeds in a suicidal attempt, some of which were masticated. Three hours later he developed severe diarrhoea with vomiting and abdominal cramps, followed by extracellular dehydration and circulatory collapse. 2 Biological changes included haemoconcentration. He recovered following symptomatic treatment by infusion of saline and glucose solutions. 3 Ricin was quantified by a radioimmunologic method using Iodine 125, and showed that only a small part of the ricin contained in the seeds was absorbed.