CARINAMIDE (4'-CARBOXYPHENYLMETHANESULFONANILIDE): ITS RENAL CLEARANCE AND BINDING ON PLASMA PROTEIN

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Abstract
The expts. presented herein indicated that considerable amts. of carinamide [previously known as caronam-ide] and its metabolite (s) were adsorbed on plasma protein. They were adsorbed to the same extent and the adsorption curves corresponded to the typical adsorption isotherm. Desorption of the compounds from plasma protein readily occurred. A reciprocal relationship between the plasma concn. and the clearance ratio or excretion ratio for carinamide and total carinamide was found to exist. The clearance ratios for carinamide and total carinamide never exceeded 1 at any plasma concn.; however, their excretion ratios ("corrected" clearance ratios) fluctuated widely from greater than 2 to less than 0.5, although they were the same for the 2 forms of the drug at similar plasma concns. PAH at high plasma concns. markedly reduced both ratios regardless of whether the excretion ratio was greater or less than 1. It seems certain, therefore, that a large portion of the drug filtered at the glomeruli is reabsorbed by the renal tubules. However, it is evident that at low plasma concns. glomerular filtration of the drug calculated as "unbound" in plasma water is inadequate to account for the amt. of drug excreted per unit time. It has been proposed that plasma binding, or the electrostatic attraction between plasma protein and carinamide, impedes the amt. of drug filtered on a temporal basis but does not limit filtration to the amt. detd. in a static in vitro system as unbound. Alternatively, it may be that both tubular secretion and reabsorption of the drug occurs. The inhibition by PAH may be reconciled with either alternative hypothesis.
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