[Peganum harmala L. poisoning and pregnancy: two cases in Morocco]. / Intoxication au Peganum harmala L. et grossesse : deux observations marocaines.

Peganum harmala L. (wild or Syrian rue) is commonly used as an emmenagogue and abortifacient in traditional medicine in the Middle East and North Africa including Morocco. The purpose of this report is to describe two cases of Peganum harmala L. poisoning in pregnant women. Both cases were treated successfully with good maternal-fetal outcome good for mother and child.

Determination of unbound platinum after oxaliplatin administration: comparison of currently available methods and influence of various parameters.

Variations in plasma protein binding may have profound effects on both disposition and activity of drugs, especially for those which are tightly bound to proteins, such as anticancer platinum derivatives. Methods of separation of the non-protein-bound fraction and some technical parameters may influence the results. We have compared ultrafiltration and ultracentrifugation, as well as the effect of potentially interfering factors, upon the determination of the plasma unbound platinum fraction after oxaliplatin administration to cancer patients. Ultrafiltration and ultracentrifugation provided very closely correlated results, so that either technique can be used. The ultrafiltration cut-off (3000-30,000 Da) devices, the type of tube for blood sampling and the type of anticoagulant (none, lithium heparinate or EDTA) did not influence the results markedly. In contrast, results were greatly influenced by freezing: erratic results were obtained on thawed plasmas when compared with those on fresh serum or plasma. Consequences may be important in usual practice, since many pharmacokinetic studies are carried out in multicentric trials with plasma processing centralized in one reference laboratory. The methods for the determination of protein-drug binding should be standardized and guidelines elaborated where optimal conditions for each type of binding assay are given.

[Acute cardiac toxicity of 5-fluorouracil: pharmacokinetic correlation]. / Toxicité cardiaque aiguë du 5-fluorouracile: corrélation pharmacocinétique.

High-dose 5-fluorouracil (5-FU) continuous infusion over a 4-day period seems to dramatically increase the frequency of cardiac complications, which were however extremely rare in the past when it was injected in bolus form (1.6%). In order to evaluate their real incidence we looked for a relation between cardiac toxicity and clinical or 5 FU pharmacokinetic parameters. One hundred and thirty-three patients were followed up from January 1989 to March 1990, treated for head and neck, breast and colorectal cancers by high-dose 5-FU infusion (1,000 mg/sqm/d x 4 d) and cis-platinum (20 mg/sqm/d x 4 d). During each treatment course, daily electrocardiogram and 5 FU plasma assays were performed by high performance liquid chromatography, at 8 am and 8 pm. Twenty-eight patients presented 36 ischemic cardiac manifestations which were sometimes severe. Of these, 29 were asymptomatic. Cardiac toxicity frequency was not increased in the group treated for head and neck cancers. Pharmacokinetic analysis showed wide variations in 5-FU plasma levels in the 133 patients under study (from 20 to 1,200 ng/ml). Cardiac manifestations always appeared during the hours following very high 5-FU plasma levels (greater than 450 ng/ml). Cardiotoxicity seems to be linked to 5-FU plasma levels. Cis-platinum probably increases toxicity in this regimen. These findings indicate the advisability of a close follow-up by daily ECG when 5-FU is administered at high doses in continuous infusion and associated with cis-platinum. We are continuing to study 5 FU cardiac toxicity, especially in other regimens containing 5 FU and aim to evaluate the contribution of cardiac isotopic exams.

Screening for neutral and basic drugs in blood by dual fused-silica column chromatography with nitrogen-phosphorus detection.

We describe a capillary gas-chromatographic method for detection and quantification of basic and neutral drugs in the plasma of patients thought to be poisoned after dangerous overdose. Without further derivatization, the drugs are extracted from 1 mL of plasma, at basic pH, into diethyl ether. The extracts are injected onto two fused-silica capillary columns of different polarity (Ultra 1 and CP Sil 19 CB) coupled to nitrogen-phosphorus detectors. Under these conditions, drug-free plasmas give blank chromatograms, with a peak only for the internal standard (RN 927, an antihistamine not being marketed). Plasma samples from patients who have taken drugs show additional peaks, the relative retention times (RRTs) of which are used to identify the drugs. Here we list the RRTs of about 200 drugs on the two columns. Analyses are routinely performed with an automatic injector; overall analysis time is about 1 h per sample. During the last six years, more than 1000 plasma samples per year have been analyzed. We find this method a powerful tool for toxicological analysis, especially in cases of multi-drug intoxications.