Studies of Sulfobromophthalein Sodium (BSP) Metabolism in Man. II. The Effect of Artificially Induced Fever, Norethandrolone (Nilevar), and Iopanoic Acid (Telapaque)*

Abstract

The disappearance of sulfobromophthalein sodium (BSP) from the blood after its intravenous administration is a result of a complex of processes-hepatic uptake, storage, conjugation, and biliary excretion of the dye (1). Fever and the administration of anabolic steroids are among the factors that may influence the metabolism of BSP.In an attempt to determine the mechanisms of abnormal BSP retention induced by anabolic steroids and fever, we studied the effects of norethandrolone (Nilevar)' and of a brief period of artificially induced fever upon transport of the dye. During compilation of normal values for fractional clearance of BSP (2), a depression of this transport parameter was encountered in a woman ultimately given the diagnosis of "irritablebowel syndrome." When we learned that the gallbladder contrast medium, iopanoic acid (Telepaque),2 had been ingested on the evening before study, we added to the original plan an investigation of the effect of this commonly used cholecystographic material on BSP metabolism. Consequently, this paper reports observations on alteration of BSP transport induced by artificial fever and by two chemical agents, norethandrolone and iopanoic acid. MethodsThe methods used for measuring the fractional clearance (percentage disappearance rate, PDR), retention of dye at 60 minutes, and the proportion of serum BSP found in conjugated forms after a single intravenous * Submitted for publication December 23, 1963; accepted February 27, 1964. This investigation was supported in part by research grant AM-06908 from the National Institutes of Health. injection of the dye have been described previously (2). Measurement of maximal biliary excretion (Tm) and relative hepatic storage capacity (S) for BSP during its constant infusion have been described also (2, 3). In all instances normal healthy subjects were studied. Fever. Fractional clearance, retention of the dye at 60 minutes, and proportion of serum BSP in conjugates after a single intravenous injection of the dye were determined in six subjects. Each subject was studied on three occasions: at least one day before artificially induced fever, during the febrile episode, and the day after.The subject was placed supine in a moist-heat, feverproducing cabinet with only his-head exposed. About 1 hour was required to elevate the body temperature to 103°F as recorded by an electrical rectal thermometer. This temperature was maintained for the determination of fractional clearance and then permitted to drift back toward normal. In most instances the temperature was about 2°F above the base-line level at the time the 1-hour blood sample was drawn for determination of BSP retention.Tm and S for BSP were estimated in two additional healthy individuals with use of the constant-infusion technic of Wheeler, Meltzer, and Bradley (3). Fever was induced as described above, and rectal temperature greater than 1030 F was maintained for about 45 minutes, the total febrile period being about 3i hours. The constant infusion was started when the temperat...

The Incidence and Significance of Liver Dysfunction in Crohn’s Disease

“…Excretion of BSP becomes progressively less efficient in subjects over the age of 50 years [30] but the patients in this study were mainly drawn D yer/Dawson from the younger age groups. Artificially induced fever may also impair BSP excretion [17] although this is not invariable [25], It is, therefore, of inteiest that the presence of pyrexia correlated with the more severe degrees of impairment of BSP retention in this study, although afebrile patients fre quently showed mildly abnormal results. This suggests that fever may aggravate the hepatic dysfunction caused by the bowel disease.…”

Application of Clearance and Volume of Distribution to the Plateau Principles of Drugs

“…21) would indicate that methandrostenolone is capable of displacing oxyphenbutazone from extravascular binding sites. Norethandrolone and iopanoic acid appear capable of inhibiting liver storage and excretion of BSP in man (11). It is possible that this is a reflection of competition for liver binding sites.…”

Sulphobromophthalein retention in gout and asymptomatic hyperuricaemia.

“…Elevation of BSP retention also occurs in cardiac failure (Felder, Mund, and Parker, 1950;Richman, Delman, and Grob, 1961), old age (Rafsky and Newman, 1943), alcoholism (Leevy and others, 1953), infections (Neale, Caughey, Mollin, and Booth, 1966), malaria (Machella, 1947), artificially-induced fever (Bradley and Conan, 1947;Hicks, Holt, Guerrant, and Leavell, 1948), obesity (Zelman, 1952), starvation (Rozental, Biava, Spencer, andZimmerman, 1967), after extra-abdominal surgery (Tagnon, Robbins, and Nichols, 1948), and after the use of the gall-bladder contrast medium iopanoic acid "Telepaque" and the anabolic steroid drug norethandrolone "Nilivar" (Schoenfeld and Foulk, 1964). Abnormal BSP retention has also been stated to occur after exercise, in hyperthyroidism, Cushing's disease, and ulcerative colitis (Cohn, 1965).…”