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Inhibition of Folate Metabolism in Chemotherapy pp 229–242Cite as

Clinical Pharmacokinetics of Co-trimoxazole

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 64))

Abstract

Co-trimoxazole is a combination drug of trimethoprim (TMP) and sulfamethoxazole (SMX) in a 1: 5 ratio. This combination interferes with two consecutive steps in the normal bacterial metabolism of folinic acid. All sulfonamides competitively inhibit the utilization of p-aminobenzoic acid (pABA) in the synthesis of dihydrofolic acid. Since humans do not synthesize dihydrofolic acid but depend on dietary sources for their needs, this inhibition occurs only in the microorganism. TMP blocks the conversion of dihydrofolic acid to tetrahydrofolic acid (folinic acid) by inactivating the enzyme dihydrofolate reductase. This reaction occurs both in humans and in microorganisms, but the enzyme system of the microorganism is 10,000–50,000 times more sensitive than the corresponding mammalian system (Chap 1). The synergistic, bactericidal effect of the combination TMP/SMX has been demonstrated (Böhni 1969; Darell et al. 1968; Dornbusch 1971; Schwartz and Rieder 1970) in a wide variety of gram-positive and gram-negative organisms. The effect is maximal at a TMP/SMX ratio between 1: 5 and 1:40, depending on the parasite involved (see also Chap. 4).

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  1. The Wellcome Research Laboratories, Burroughs Wellcome Co., 3030 Cornwallis Road, Research Triangle Park, 27709, NC, USA

    George H. Hitchings

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Hansen, I. (1983). Clinical Pharmacokinetics of Co-trimoxazole. In: Hitchings, G.H. (eds) Inhibition of Folate Metabolism in Chemotherapy. Handbook of Experimental Pharmacology, vol 64. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-81890-5_11

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