SODIUM IOTHALAMATE, ANGIO-CONRAY, IN SELECTIVE ANGIOGRAPHY: FURTHER EVIDENCE OF LOW TOXICITY.
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The effects of the iodine-containing radiocontrast agents ipodate, iopanoic acid, and iothalamate on the secretion of T4, T3, and rT3 were studied using perfused canine thyroid lobes. The experiments were performed as paired comparisons, with one thyroid lobe acting as a control. At 10(-5) M, the two agents used for cholecystography (ipodate and iopanoic acid) inhibited the TSH-stimulated secretion of T3 [ipodate, 69 +/- 8% of control (P less than 0.05); mean +/- SE; n =4] and rT2 [iopanoic acid 59 +/- 9% (P less than 0.01); iopanoic acid, 61 +/- 9% (P less than 0.05)], whereas T4 secretion was not significantly altered. Iothalamate (10(-3)M), an agent predominantly excreted through the kidneys, did not alter T4, T3, or rT3 secretion. This pattern is compatible with an inhibitory effect on intrathyroidal T4 deiodination to T3 and rT3 by ipodate and iopanoic acid, similar to the inhibition of T3 deiodinases in peripheral tissues by these compounds. At a concentration of 10(-3) M, ipodate induced a hitherto unrecognized pattern of thyroid hormone secretion: a very rapid, sustained and reversible inhibition of the secretion of all three iodothyronines. The mechanism behind this response remains to be elucidated.
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A high-performance liquid chromatographic (HPLC) assay method has been developed for the quantitative determination of iothalamate and p-aminohippuric acid (PAH) concentrations in serum and urine samples in the male rat. Glomerular filtration rate (GFR) was measured as clearance of iothalamate, while effective renal blood flow (ERBF) was measured as clearance of PAH. The method is simple, rapid and sensitive and detects iothalamate and PAH in rat serum and urine following administration of bolus doses and continuous infusions of iothalamate and PAH. Samples of serum and urine were deproteinized with two volumes of acetonitrile containing the internal standard, and an aliquot chromatographed on a C18 reversed-phase column. The mobile phase was comprised of 0.1 M sodium phosphate with 1.2 mM tetrabutylammonium phosphate: methanol, 85:15 (v/v), at a flow rate of 1.0 mL/min. The analytical column eluate was monitored with a UV detector at 254 nm with quantitation achieved using peak-height ratios. The precision of the method was 6.6 and 3.6% for iothalamate in serum and urine, and 5.6 and 4.9% for PAH in serum and urine, respectively. The lower limit of quantitation was 0.63 microgram/mL for iothalamate and 1.25 microgram/mL for PAH in serum, and 3.1 microgram/mL for iothalamate and 1.5 microgram/mL for PAH in urine. Recovery of iothalamate from serum and urine was 99.9 and 93.5%, respectively. Recovery of PAH from serum and urine was 99.8 and 92.6%, respectively. The present study demonstrated that non-radioactive iothalamate and PAH can be measured simultaneously using a HPLC assay to measure GFR and ERBF in the male rat.
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