Abstract
The authors evaluated the relationships among renal function, acetylator phenotype and serum sulfadiazine levels in 22 patients with paracoccidioidomycosis treated with 1 tablet of cotrimazine (a combination of 820 mg sulfadiazine and 180 mg trimethoprim) administered orally every 12 hours.
Fifteen patients (68.18%) presented free sulfadiazine levels above 50 μg/ml, 6(27.28%) presented serum levels above 40 μg/ml, and 1(4.54%), levels lower than 40 μg/ml, this being the patient in which treatment failed. The highest free sulfadiazine levels were obtained in slow acetylator patients with reduced renal function. One patient with neuroparacoccidioidomycosis presented free sulfadiazine levels in cerebrospinal fluid corresponding to 55% of the serum levels.
Finally, the authors consider cotrimazine to be an important therapeutic alternative for neuroparacoccidioidomycosis and conclude that administration every 12 hours can provide therapeutic sulfadiazine levels. They also suggest that when the sulfadiazine-trimethoprim combination is used, the therapeutic levels of sulfadiazine should be above 40 μg/ml.
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References
Barbosa W, Daher RR. Blastomicose Sul Americana (Paracoccidioidomicose). In: Veronesi, R. Doenças Infecciosas e Parasitárias. 7 ed. Rio de Janeiro, Guanabara Koogan, 1982; p. 638–651.
Barbosa W. Vasconcellos WM de P.V. Ação da sulfametoxazol associada ao trimetoprim na terapêutica da Blastomicose Sul Americana. Rev Pat trop 1973; 2: 329–339.
Barraviera B, Mendes RP, Machado JM, Pereira PCM, Souza JM, Meira DA. Evaluation of treatment of para-coccidioidomycosis with cotrimazine (combination of sulfadiazine and trimethoprim). Rev Inst Med trop S Paulo 1989; 31: 53–5.
Beiguelman B. Farmacogenética e sistemas sanguíneos eritrocitários. Guanabara Koogan, Rio de Janeiro 1983; 192 p.
Beiguelman B, Ramalho AS, Arena JFP, Garlipp CR. A acetilação da isoniazida em brasileiros caucasóides e negróides com tuberculose pulmonar. Rev Paul Med 1977; 89: 12–15.
Bergan T, Brodwall EK, Vik-Mo H, Anstad U. Pharmacokinetics of sulphadiazine, sulphamethoxazole and trimethoprim in patients with varying renal function. Infection 1979; 7 (supl. 4): S382–386.
Bergan T, Vik-Mo H, Anstad U. Kinetics of a sulfadiazine-trimethoprim combination. Clin Pharmacol Ther 1977; 22: 211–224.
Bratton AC, Marshall EK. A new coupling component for sulfanilamide. J Biol Chem 1939; 128: 537–550.
Budel AR, Fernandes GP, Lameira RF, Telles Filho FO. Sensibilidade ‘in vitro’ do Paracoccidioides brasiliensis à associação trimethoprim-sulfametoxazol. Rev Soc Bras Med trop 1987; 20 (supl.): 76.
Del Negro G. Tratamento. Controle de cura. Profilaxia. In: Del Negro G, Lacaz CS, Fiorillo AM. Paracoccidioidomicose (Blastomicose Sul Americana). Sarvier, EDUSP, S. Paulo 1982; p. 271–283.
Drutz DJ. Paracoccidioidomycosis. In: Wyngaarden JB, Smith LH. Cecil Textbook of Medicine. WB Saunders Company, Philadelphia, 18th ed., 1988; p. 1843–1844.
Eidus L, Varughese P, Hodgkin MM, Hsu AHE, McRae KB. Simplification of isoniazid phenotyping procedure to promote its application in the chemotherapy of tuberculosis. Bull WHO 1973; 49: 507–516.
Franco MF, Montenegro MR, Mendes RP, Marques SA, Dillon NL, Motta NGS. Paracoccidioidomycosis: a recently proposed classification of its clinical forms. Rev Soc Bras Med trop 1987; 20: 129–132.
Guerreiro CAM, Chuluc SSD, Branchini MLN. A new treatment for large cerebral paracoccidioidomycosis. Arq Neuro-Psiquit 1987; 45: 419–423.
Harvey SC. Antimicrobial drugs. In: Remington's Pharmaceutical Sciences. Philadelphia College of Pharmacy and Science, 16th ed. 1980; p. 1099–1178.
Hodgkin MM, Eidus L, Hamilton EJ. Screening of isoniazid inactivators by dilution test. Bull WHO 1974; 51: 428–430.
Mandell GL, Sande MA. Antimicrobial agents. In: Goodman and Oilman's. The Pharmacological basis of therapeutics. MacMillan Publishing Company, New York, 7th ed., 1985; p. 1095–1114.
Mendes RP. Paracoccidioidomicose. In: Meira DA. Terapêutica de Doenças Infecciosas e Parasitárias. Rio de Janeiro, EPUME, 1987; p. 175–182.
Motulsky A. Pharmacogenetics. Progr Med Genet 1964; 3: 49–74.
Padilha-Gonçalves A. Estudo das concentrações sanguíneas das sulfonamidas no decurso do tratamento da Blastomicose brasileira. O Hospital 1946; 29: 875–881.
Paolucci AA. Exploração clínica da função renal. Nefrologia, Guanabara Koogan, Rio de Janeiro 1977; p. 63–71.
Ribeiro DO. Nova terapêutica para a Blastomicose. Publ Med (S. Paulo) 1940; 12: 36–54.
Snedecor GW, Cochran WG. Statistical methods. Ames. Iowa State University, 7 ed. 1980; 505 p.
Sunahara S, Urano M, Ogawa M. Genetical and geographical studies in isoniazid inactivation. Science 1961; 134: 1530–1531.
Vree TB, O'Reilly WJ, Hekster YA, Damsma JE, Van der Kleijn E. Determination of the acetylator phenotype and pharmacokinetics of some sulphonamides in man. Clin Pharmacokinet 1980; 5: 274–294.
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Barraviera, B., Pereira, P.C.M., Mendes, R.P. et al. Evaluation of acetylator phenotype, renal function and serum sulfadiazine levels in patients with paracoccidioidomycosis treated with cotrimazine (a combination of sulfadiazine and trimethoprim). Mycopathologia 108, 107–112 (1989). https://doi.org/10.1007/BF00436060
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DOI: https://doi.org/10.1007/BF00436060