Determination of the acetylator phenotype in Moroccan tuberculosis patients using isoniazid as metabolic probe.

A large interindividual variability in drug acetylation is associated with genetic polymorphism of the polymorphic Type 2 N-acetyltransferase (NAT2), and an important interethnic difference has been frequently observed. However, few data on this polymorphism in the Moroccan population are available. In the present study the acetylator phenotype in 89 Moroccan patients with tuberculosis has been determined using isoniazid (INH) as metabolic probe. The subjects (69 women and 20 men between 18 and 77) were each given a 5 mg/kg oral dose of INH. Plasma concentration of INH and its metabolite, acetylisoniazid (ac.INH), were measured by high-performance liquid chromatography at 3 hours post dose. The plasma level ratio of acetylisoniazid to isoniazid (Rm), and the plasma level of acetylisoniazid as a percentage (%ac.INH) were used to express the activity of the polymorphic NAT2. The distribution of these 2 parameters in the studied population was clearly bimodal resulting in 2 distinct groups: slow acetylators (Rm < or = 0.84, %ac.INH < or = 45.64%), and fast acetylators (Rm > or = 1.29, %ac.INH > or = 56.26%) who accounted respectively for 61.8% and 38.2% of the population. The 2 approaches used showed a complete concordance.

Therapeutic isoniazid monitoring using a simple high-performance liquid chromatographic method with ultraviolet detection.

Simultaneous measurement of isoniazid and its main acetylated metabolite acetylisoniazid in human plasma is realized by high-performance liquid chromatography. The technique used is evaluated by a factorial design of validation that proved to be convenient for routine drug monitoring. Plasma samples are deproteinized by trichloroacetic acid and then the analytes are separated on a microBondapak C18 column (Waters). Nicotinamide is used as an internal standard. The mobile phase is 0.05 M ammonium acetate buffer (pH 6)-acetonitrile (99:1, v/v). The detection is by ultraviolet absorbance at 275 nm. The validation, using the factorial design allows one to: (a) test the systematic factors of bias (linearity and matrix effect); (b) estimate the relative standard deviations (RSDs) related to extraction, measure and sessions assay. The linearity is confirmed to be within a range of 0.5 to 8 microg/ml of isoniazid and 1 to 16 microg/ml of acetylisoniazid. This method shows a good repeatability for both extraction and measurement (RSD INH=3.54% and 3.32%; RSD Ac.INH=0.00% and 5.97%), as well as a good intermediate precision (RSD INH=7.96%; RSD Ac.INH=15.86%). The method is also selective in cases of polytherapy as many drugs are associated (rifampicin, ethambutol, pyrazinamide, streptomycin). The matrix effect (plasma vs. water) is negligible for INH (3%), but statistically significant for Ac.INH (11%). The application of this validation design gave us the possibility to set up an easy and suitable method for INH therapeutic monitoring.

Blood cadmium concentration in the population of the Rabat area, Morocco.

Blood cadmium concentrations were determined in 377 adults, 297 men and 80 women, randomly selected from the Rabat Transfusion Center, Morocco. The mean blood cadmium level was 1.1+/-0.7 microg/l, which was higher than in French subjects, with an average of 0.7+/-0.6 microg/l. In Moroccan people, the mean blood cadmium concentration of men, 1.1+/-0.8 microg/l, was significantly higher than that of women, 0.8+/-0.4 microg/l, whereas in the French people tested, there was no statistically significant difference between men and women. In Morocco, employment of men and the smoking habits of men and women were linked to an increase of blood cadmium levels. The significantly higher level observed in men could be due to a higher percentage of men who were smokers and to professional activity leading to increased exposure to cadmium.

[Lead impregnation in inhabitants of the Rabat region (Morocco)]. / Etude de l'imprégnation saturnine des habitants de la région de Rabat (Maroc).

OBJECTIVES: No current data is available on plumbism in Morocco. We conducted this work to evaluate blood lead levels in inhabitants of the Rabat region. PATIENTS AND METHODS: The study included 385 subjects, 300 men and 85 women, age range 18-55 years, who were volunteer blood donors at the Rabat blood bank. All subjects responded to a short questionnaire concerning type of lodging cigarette smoking, occupation. Blood lead levels were assayed by inductively coupled plasma-mass spectrometry (ICPMS). RESULTS: Mean blood lead levels for all subjects was 86.9 +/- 42.1 micrograms/l (92.9 +/- 51.7 micrograms/l for men and 80.9 +/- 32.6 micrograms/l for women). Blood lead levels increased more rapidly with age in women than in men. Levels in subjects who lived in residential urban areas were lower than those living in the old Arab center. Levels were higher in smokers than in non-smokers and in subjects with an employment than in those without. CONCLUSION: Mean blood lead levels in the Rabat region are similar to those currently observed in other countries where this same type of study has been conducted. Similar factors are associated with high mean blood lead levels.