Dosage Regimen Calculation of Chemotherapeutic Agents. Part. III Sulfasymazine

Krüger-Thiemer, Ekkehard; Bünger, Paul; Dettli, L; Spring, P; Wempe, E

doi:10.1159/000220426

Cited by 17 publications

(5 citation statements)

References 3 publications

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“…6Antibacterial activities have been reported previously17'30 or were newly determined by the same method. 26 In the cases where new determinations were made the values given are the average values obtained from all the determinations. "The determination of the physicochemical parameters which have been used is reported elsewhere.17'30 ^Determination from an experiment in which only 2 concentrations of the drug were utilized (Figure 5).…”

Section: Methodsmentioning

confidence: 99%

Sulfonamide structure-activity relation in a cell-free system. Correlation of inhibition of folate synthesis with antibacterial activity and physicochemical parameters

Miller¹,

Doukas²,

Seydel³

1972

J. Med. Chem.

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Various physicochemical parameters (p , Hammett a, chemical shift, and ) of two series of substituted sulfonamides (IV'-phenyl and V'-pyridyl) have been correlated to their inhibitory activities in a cell-free folate-synthesizing system. The rate-determining steps for sulfonamide action in the cell-free system and a whole cell system were found to have similar substituent dependencies, indicating the likelihood of a common reaction. Comparison of the linear free energy relationships obtained in the two systems indicates that the common parabolic dependency of sulfonamide antibacterial activity is best explained by the Brueckner and Cowles theory rather than the more commonly used Bell and Roblin theory. Permeability of the bacteria to these sulfonamides in the whole cell system was found to be unimportant unless they were present in the ionized form to an extent greater than 90%. The data indicate that lipophilic factors-characterized by -are not important in the cell-free system, nor are they important in determining antibacterial in vitro activity when permeability is not limited by ionization.The relationship of the chemical structure of medicinal agents to their biological activity is a fundamental problem of science. Sulfonamides have played a leading role in our current understanding of this relationship. In a pioneering paper Woods1 recognized in 1940 that the antibacterial activities of sulfonamides were antagonized by the structurally similar compound, p-aminobenzoic acid (PABA).Bell and Roblin,2 Brueckner,3 and Cowles4 soon realized that the antibacterial activities were related to the acid dissociation constants of the sulfonamide groups. They postulated the existence of a critical 10 mM MgQ2; 50 mM 2-mercaptoethanol; 1 mM ATP; 20 µ PABA; 40 µ dihydropterin alcohol; sulfonamide as required; and 300 Mg

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Section: Methodsmentioning

confidence: 99%

Sulfonamide structure-activity relation in a cell-free system. Correlation of inhibition of folate synthesis with antibacterial activity and physicochemical parameters

Miller¹,

Doukas²,

Seydel³

1972

J. Med. Chem.

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show abstract

“…He showed that when human serum was injected into the pleural cavity, distribution into this compartment occurred to a much greater extent than when saline controls were injected. Johnson et Journut of Pharmaceutical Sciences (193) and Kriiger-Thiemer et al (194). Other workers (195,196) failed to observe this effect, but it should be noted that their experimental methods employed rather large dilutions of plasma samples with concomitant pertubation of binding equilibria.…”

Section: Andmentioning

confidence: 98%

The Binding of Drugs by Plasma Proteins

Meyer¹,

Guttman²

1968

Journal of Pharmaceutical Sciences

373

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“…Since only free drug can be removed by the kidney or metabolized, protein binding of sulfadimethoxine should extensively affect sulfadimethoxine disposition. Kruger-Thiemer et al (9) proposed a number of pharmacokinetic models involving protein binding of sulfonamides in humans. By means of computer simulations, these authors fit the plasma concentration uersus time data to a pharmacokinetic model involving protein binding.…”

Section: Resultsmentioning

confidence: 99%