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Pharmacokinetics of sulfametopyrazine (Kelfizine W) effects of a single oral dose

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Summary

The pharmacokinetics of sulfametopyrazine were studied for seven days after a single oral dose of 2 g. in healthy volunteers in order to establish its chemotherapeutic value. — The appearance and disappearance of the drug in the plasma were evaluated both for compounds with a free amino group and for total sulphonamides. The half-life and absorption, distribution, elimination and excretion coefficients were calculated, as well as the concentrations in plasma water and interstitial fluid. The estimated drug concentrations in the urine agreed with those calculated from the excretion coefficients. — In all subjects at the end of the seventh day the concentrations in all body compartments of active compounds exceeded the minimum required for a therapeutic effect. The highest concentrations found in the urine were always significantly lower than the drug's basal solubility at pH 5, thus excluding any risk of crystalluria.

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Abbreviations

β:

total binding capacity of plasma proteins for SMP

ρ:

Specific gravity of blood (ρ Bl), and interstitial fluid (ρIF)

μ:

minimum inhibitory concentration for bacterial growth. Evaluation of μ against E. coli or other pathogenic bacteria in a medium free of antagonists [29]

ε:

ratio of dose interval to half-life

τ:

dose interval

σ:

safety factor. Proportionality constant between μ andc min for a therapeutic efficacy of 95 per cent

δ′:

fraction of the administered drug absorbed from the depot (gastrointestinal tract etc.)

Δ′:

distribution coefficient with respect to the drug concentration in blood plasma (ml/g)

D*:

initial dose of the drug

D :

maintenance dose

M :

molecular weight of the drug (280)

G :

weight of subject (kg)

F :

area between time axis and concentration curve (plotted c' values)

t′ 50% :

apparent biological half-life

w 1 :

water content of plasma (ml/ml)

p :

protein concentration of plasma (pBl), or interstitial fluid (pIF) (g/l)

c′ IF :

concentration in the interstitial fluid

C′ 0 :

concentration in plasma at zero time after i.v. administration

c′ 01 :

concentration in plasma after oral absorption extrapolated to zero time

c 1 :

concentration in plasma water of the drug with free amino function

c min :

minimum inhibitory concentration needed in plasma water (minimum therapeutic concentration)

k′ 01 :

rate constant for absorption

k′ 1 :

rate constant for absorption determined at timet; (similarlyk′2)

K :

total elimination coefficient

k′ el :

rate constant for elimination

k F :

rate constant for formation of metabolites

k D :

excretion coefficient of SMP with free amino function

k U :

coefficient of metabolite excretion

D 0 :

quantity of SMP in the body at time zero

D B :

quantity of SMP in the body at timet

D U :

quantity of SMP excreted in the urine at timet

M F :

quantity of metabolites formed at timet

M B :

quantity of metabolites present in the body at timet

M U :

quantity of metabolites excreted in the urine at timet

K′ :

dissociation constant for the sulphonamide-protein complex

′:

notation for quantities related to drug concentrations in plasma, e.g. c′ (corresponding term without ′ refer to plasma water)

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Authors and Affiliations

  1. Department of Paediatrics, St. Elisabeth Ziekenhuis, Turnhout, Belgium

    A. Devriendt, F. H. Jansen & I. Weemaes

  2. Department of Internal Medicine, Academisch Ziekenhuis St. Raphaël, Leuven, Belgium

    A. Devriendt, F. H. Jansen & I. Weemaes

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  2. F. H. Jansen
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  3. I. Weemaes
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Devriendt, A., Jansen, F.H. & Weemaes, I. Pharmacokinetics of sulfametopyrazine (Kelfizine W) effects of a single oral dose. Eur J Clin Pharmacol 3, 36–42 (1970). https://doi.org/10.1007/BF00560289

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