Urinary and Fecal Excretion of Mercury in Man Following Administration of Mercurial Diuretics 1

Abstract

The widespread use of mercurial diuretics has stimulated greater interest in the metabolism of organic mercurials in man. Recently proposed regimens (1) involving frequent, even daily, administration of mercurials, have focused particular attention on the 24 hour excretion of these compounds in relation to the cumulative toxicity of any mercury which may be retained. Moreover, little is known of the mechanism for eliminating mercury in the urine and its relation to the process of diuresis. Therefore, the following aspects of mercury excretion in man were studied: 1) the 24 hour urinary and fecal excretions of mercury after repeated administration of mercurial diuretics; 2) the course of urinary mercury excretion before, during and after the period of maximal diuretic response; 3) the effects on the excretion of mercury, water and electrolytes of pretreatment with substances known to modify the response to mercurial diuretics. MATERIALS AND METHODSThese studies were carried out on 17 patients, 13 of whom were in congestive heart failure. The latter were maintained on a restricted daily sodium intake of 8 to 10 meq. The non-cardiac subjects were on a regular hospital diet. Thiomerin was the mercurial generally employed, since it has no xanthine component which might independently influence the excretion of mercury while its tubular action is similar to that of other mercurials (2 Chemical analyses of urine or blood were performed by the following methods: sodium and potassium by means of a Perkin-Elmer 52A lithium internal standard flame photometer; chloride by a modification of Sendroy's iodometric method (3) ; total mercury by the dithizone method, as modified by Gettler and Lehman (4); creatinine by Peters' (5) modification of the Folin-Wu method. RESULTSA. Excretion of mercury. The results are illustrated in Figures I through 9 and Table I. From Figure 1, showing total urinary mercury excretion of 17 subjects, several facts are evident. 1) As a result of early, relatively rapid excretion of mercury, half of the total (2 ml. = 80 mg. mercury) dose appears in the urine within 2½ to three hours. Another 20 to 40 mg. is excreted within 18 to 24 hours. 2) There is a definite retardation in mercury excretion during the first few hours after subcutaneous, as compared with intravenous, injection. Subsequently, the difference in total mercury excretion between the two routes of administration disappears. 3) Pretreatment with ammonium chloride does not influence the rate or completeness of excretion of subcutaneously or intravenously administered mercurials.Despite the fairly complete urinary excretion of mercury within 20 to 24 hours, the output of 1208

Renal Extraction and Excretion of Mercury in Man Following Intravenously Administered Mercurial Diuretics 1

“…As a consequence of the rapid early excretion of mercury, a significant fraction of the total mercury administered is eliminated before the onset of diuresis (1). However, the present chemical methods measure only total mercury in the blood and urine.…”

Factors Influencing the Course of Mercurial Diuresis During Pitressin® Infusion in Normal Subjects 12

“…Previous studies from this laboratory (17) have shown that a large fraction of intravenously administered mercury appears in the urine before diuresis has begun. More significantly, as much as % to % of the injected mercury is excreted after diuresis has subsided.…”

PLASMA REGRESSION, DISTRIBUTION AND EXCRETION OF RADIOMERCURY IN RELATION TO DIURESIS FOLLOWING THE INTRAVENOUS ADMINISTRATION OF Hg203 LABELLED CHLORMERODRIN TO THE DOG 1

“…An undetermined time lag is introduced between removal of the drug from the blood plasma and its delivery into the urine. (7,8) following the administration of Meralluride. Such rapid rates of excretion are the more surprising in view of the high degree of binding of mercurial diuretics to plasma protein (9,10).…”

“…As a first approximation, it is reasonable to assume that the drug exerts its characteristic diuretic action where it is specifically and most highly concentrated. 8 Accordingly we have attempted to correlate diuresis with the accumulation of radiomercury in the renal cortex, measured qualitatively in terms of counts per minute by a Geiger tube in contact with the kidney surface. Because of the relatively low energy of the beta emission of Hg203 (0.205 MEV), beta activity measured at the surface is derived almost exclusively from the outermost few millimeters of the cortex.…”