[Blood levels of sulfadoxine and pyrimethamine, according to the malaria-treatment response, in two municipalities of Antioquia, Colombia]. / Concentraciones sanguíneas de sulfadoxina y pirimetamina según la respuesta terapéutica antimalárica, en dos municipios de Antioquia, Colombia.

PROBLEM: There has been a constant increase in the level of therapeutic failure of the sulfadoxine-pyrimethamine (SP) combination for treating uncomplicated Plasmodium falciparum malaria. OBJECTIVE: To use high-performance liquid chromatography to quantify blood levels of SP in patients with good clinical response and in patients who did not respond to treatment. METHODS: This experimental study was carried out in 2002 in Turbo and Zaragoza, two municipalities in the department of Antioquia in Colombia. There were 79 patients (45 in Turbo and 34 in Zaragoza), including both men and women, who ranged in age from 1 year to 60 years. All the patients had uncomplicated Plasmodium falciparum malaria, with a parasite density of 500 to 50,000 parasites/microL. The patients were each randomly assigned to a treatment group. The treatment groups were not blinded; the physician who provided the medication also evaluated the therapeutic response. The treatment consisted of a single combination dose of sulfadoxine (25 mg/kg) and pyrimethamine (1.25 mg/kg) in tablets (500 mg of sulfadoxine and 25 mg of pyrimethamine). Clinical-parasitological follow-up was carried out for 21 days. Blood levels of sulfadoxine and pyrimethamine were measured two hours after the treatment was given and also the day of treatment failure, if that occurred. RESULTS: Two hours after the treatment was given, the median blood level of sulfadoxine was 136.6 micromol/L in the patients who later showed a good clinical response, and it was 103.4 micromol/L among those who did not respond to treatment (P = 0.13). The medians for pyrimethamine were 848.4 nmol/L in patients with a good clinical response and 786.1 nmol/L in patients with treatment failure (P = 0.40). There were no significant differences in drug levels between the early-failure cases and the late-failure cases. The linear correlation between the blood levels of sulfadoxine and pyrimethamine was close to zero (r = 0.13). CONCLUSIONS: Between 1998 and 2002, treatment failure with the SP combination increased from 13% to 22% in Turbo, and from 9% to 26% in Zaragoza. The lack of response in 2002 could not be explained by lower blood levels of the medications.

Concentraciones sanguíneas de sulfadoxina y pirimetamina según la respuesta terapéutica antimalárica, en dos municipios de Antioquia, Colombia / Blood levels of sulfadoxine and pyrimethamine, according to the malaria-treatment response, in two municipalities of Antioquia, Colombia

PROBLEMA: Se ha observado un aumento constante del índice de fracaso terapéutico de la combinación sulfadoxina-pirimetamina (SDX-PIR) en el tratamiento de la malaria por Plasmodium falciparum sin complicaciones. OBJETIVO: Cuantificar, mediante cromatografía de líquidos de alta resolución (HPLC), las concentraciones sanguíneas de SDX-PIR en pacientes con buena respuesta clínica y sin respuesta al tratamiento. MÉTODOS: En 2002 se llevó a cabo un estudio experimental con asignación aleatoria y sin anonimato para evaluar el tratamiento con la combinación SDX-PIR en una población de 79 pacientes de dos municipios del departamento de Antioquia en Colombia (Turbo: 45; Zaragoza: 34), de uno y otro sexo y de 1 a 60 años de edad, con malaria por Plasmodium falciparum sin complicaciones y una densidad de parasitemia de 500 a 50 000 anillos/æL. El tratamiento consistió en una sola dosis, administrada bajo supervisión médica, de SDX (25 mg/kg) y PIR (1,25 mg/kg) combinadas en comprimidos (500 mg y 25 mg de SDX y PIR, respectivamente) y se realizó seguimiento clínico y parasitológico por 21 días. Las concentraciones de SDX y PIR se midieron dos horas después de la administración del medicamento y el día del fracaso terapéutico en los casos en que se produjo. RESULTADOS: A las 2 horas de haberse administrado el medicamento la concentración sanguínea mediana de SDX fue de 136,6 æmol/L en los pacientes que mostraron respuesta clínica adecuada y de 103,4 æmol/L en quienes no respondieron al tratamiento (P = 0,13). La mediana de PIR fue 848,4 y 786,1 nmol/L en pacientes con respuesta clínica adecuada y fracaso terapéutico, respectivamente (P = 0,40). Las concentraciones tampoco mostraron diferencia significativa entre los casos de fracaso temprano y tardío. La correlación lineal entre las concentraciones de SDX y PIR fue cercana a cero (r = 0,13). DISCUSION Y CONCLUSIONES: Con respecto a 1998, el fracaso del tratamiento con la combinación SDX-PIR aumentó de 13 por ciento a 22 por ciento en Turbo y de 9 por ciento a 26 por ciento en Zaragoza. La falta de respuesta en 2002 no pudo explicarse por concentraciones (menores) de los medicamentos en sangre.

Problem. There has been a constant increase in the level of therapeutic failure of the sulfadoxine-pyrimethamine (SP) combination for treating uncomplicated Plasmodium falciparum malaria. Objective. To use high-performance liquid chromatography to quantify blood levels of SP in patients with good clinical response and in patients who did not respond to treatment. Methods. This experimental study was carried out in 2002 in Turbo and Zaragoza, two municipalities in the department of Antioquia in Colombia. There were 79 patients (45 in Turbo and 34 in Zaragoza), including both men and women, who ranged in age from 1 year to 60 years. All the patients had uncomplicated Plasmodium falciparum malaria, with a parasite density of 500 to 50 000 parasites/µL. The patients were each randomly assigned to a treatment group. The treatment groups were not blinded; the physician who provided the medication also evaluated the therapeutic response. The treatment consisted of a single combination dose of sulfadoxine (25 mg/kg) and pyrimethamine (1.25 mg/kg) in tablets (500 mg of sulfadoxine and 25 mg of pyrimethamine). Clinical-parasitological follow-up was carried out for 21 days. Blood levels of sulfadoxine and pyrimethamine were measured two hours after the treatment was given and also the day of treatment failure, if that occurred. Results. Two hours after the treatment was given, the median blood level of sulfadoxine was 136.6 µmol/L in the patients who later showed a good clinical response, and it was 103.4 µmol/L among those who did not respond to treatment (P = 0.13). The medians for pyrimethamine were 848.4 nmol/L in patients with a good clinical response and 786.1 nmol/L in patients with treatment failure (P = 0.40). There were no significant differences in drug levels between the early-failure cases and the latefailure cases. The linear correlation between the blood levels of sulfadoxine and pyrimethamine was close to zero (r = 0.13). Conclusions. Between 1998 and 2002, treatment failure with the SP combination increased from 13% to 22% in Turbo, and from 9% to 26% in Zaragoza. The lack of response in 2002 could not be explained by lower blood levels of the medications

Isoniazid acetylating phenotype in patients with paracoccidioidomycosis and its relationship with serum sulfadoxin levels, glucose-6-phosphate dehydrogenase and glutathione reductase activities.

The authors evaluated the isoniazid acetylating phenotype and measured hematocrit, hemoglobin, glucose-6-phosphate dehydrogenase and glutathione reductase activities plus serum sulfadoxin levels in 39 patients with paracoccidioidomycosis (33 males and 6 females) aged 17 to 58 years. Twenty one (53.84%) of the patients presented a slow acetylating phenotype and 18(46.16%) a fast acetylating phenotype. Glucose-6-phosphate-dehydrogenase (G6PD) activity was decreased in 5(23.80%) slow acetylators and in 4(22.22%) fast acetylators. Glutathione reductase activity was decreased in 14(66.66%) slow acetylators and in 12(66.66%) fast acetylators. Serum levels of free and total sulfadoxin were higher in slow acetylator (p less than 0.02). Analysis of the results permitted us to conclude that serum sulfadoxin levels are related to the acetylator phenotype. Furthermore, sulfadoxin levels were always above 50 micrograms/ml, a value considered therapeutic. Glutathione reductase deficiency observed in 66% of patients may be related to the intestinal malabsorption of nutrients, among them riboflavin, a FAD precursor vitamin, in patients with paracoceidioidomycosis.