A comparison of the dissolution profiles for several commercially available [131I]sodium iodide capsules

The dissolution profiles for [¹³¹I]sodium iodide diagnostic capsules from three commercial vendors were studied. The ¹³¹I release rate in water was rapid for capsules from Vendors A and C. The dissolution profile for the Vendor B product resembled that of a sustained release capsule. The data from the study indicates the potential for differences in the bioavailability of ¹³¹I from the sodium iodide diagnostic capsules.     

Evidence for a secretion of thyroxine by isolated hog thyroid cells

Isolated thyroid cells prepared from hog thyroid glands by tryptic dispersion were incubated with ¹³¹I⁻ for 1–6 h. Free [¹³¹I]thyroxine was identified in the incubation medium by three chromatographic methods. Neither [¹³¹I]iodotyurosines nor [¹³¹I]triiodothyronine were detected. The [¹³¹I]thyroxine released in the medium by 100 μl of cells (packed cell volume) after a 6-h incubation period amounted to 1.16% (S.E. = ± 0.39) of the total radioactivity. The medium [¹³¹I]thyroxine represented 15–25% of the total [¹³¹I]thyroxine synthesized during the 6 h of incubation. Thyrotropin, 1–60 munits/ml, increased the medium [¹³¹I]thyroxine content 2–4 fold. Dibutyryl cyclic AMP mimicked the effect of thyrotropin. The amount of medium [¹³¹I]thyroxine was strictly related to the amount of incubated cells but was independent of the volume of the incubation medium. When prelabeled cells were incubated in the presence of methimazole the increase in medium [¹³¹I]thyroxine was quantitatively related to a decrease in the intracellular [¹³¹I]thyroxine. Addition of dinitrotyrosine, an inhibitor of the deiodinase activity, induced the release of iodotyrosines in the incubation medium. That the incubation supernatant of isolated thyroid cells did contain free thyroxine but no iodotyrosines suggests that the normal mechanisms of proteolysis of thyroglobulin and deiodination of iodotyrosines inside the cells are preserved. From these data, it was concluded that the thyroxine release by isolated cells represents a real secretion.     

Development and Evaluation of a Novel Modified-Release Pellet-Based Tablet System for the Delivery of Loratadine and Pseudoephedrine Hydrochloride as Model Drugs

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion–spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.     

In vitro and in vivo evaluation of single-unit commercial conventional tablet and sustained-release capsules compared with multiple-unit polystyrene microparticle dosage forms of ibuprofen

The major aims of the present study were (1) to select a multiple-unit formulation that matched the in vitro dissolution profile of single-unit sustained-release commercial capsules, (2) to compare the sustaining/controlling efficacy of the selected multiple-unit formulation with that of the single-unit commercial conventional tablet and sustained-release capsules, and (3) to determine whether an in vitro-in vivo correlation exists for single- and multiple-unit formulations. Ibuprofen (20%–60% wt/wt)-loaded multiple-unit polystyrene microparticles were prepared by an emulsion-solvent evaporation method from an aqueous system. The in vitro release profiles obtained in phosphate buffer of pH 6.8 for drug-loaded polystyrene microparticles and for commercial sustained-release capsules (Fenlong-SR, 400 mg) were compared. Since the microparticles with 30% ibuprofen load showed a release profile comparable to that of the Fenlong-SR release profile, the microparticles with this drug load were considered to be the optimized/selected formulation and, therefore, were subjected to stability study and in vivo study in human volunteers. A single-dose oral bioavailability study revealed significant differences in C_max, T_max, t^1/2a, t^1/2e, K_a, K_e, and AUC between the conventional tablet and optimized or Fenlong-SR capsule dosage forms. However, all the parameters, with the exception of K_a along with relative bioavailability (F) and retard quotient (R_Δ), obtained from the optimized ibuprofenloaded microparticles were lower than that obtained from the commercial Fenlong-SR formulation. Furthermore, linear relationship obtained between the percentages dissolved and absorbed suggests a means to predict in vivo absorption by measuring in vitro dissolution. Published: September 1, 2006     

Cerebrospinal fluid flow and iodide131 transport in the spinal subarachnoid space

Free Na¹³¹ I and ¹³¹I-Albumin were injected in the cisterna magna of rhesus monkeys. The dynamics of descent into the spinal subarachnoid space and transport out of the cerebrospinal fluid were determined by gamma scintigraphy. ¹³¹I-Albumin moved slowly caudally, reaching the sacral CSF in three hours. Free Na¹³¹I was rapidly absorbed locally and did not descend. When its transport out of cerebrospinal fluid was inhibited by the addition of unlabeled isotonic Na I, ¹³¹I descended slowly at a rate parallel to that of tagged albumin. Injection of Na¹³¹I in hypertonic solutions caused immediate descent. Two minute periods of tumbling activity caused rapid movement of Na¹³¹I and ¹³¹I-Albumin into the lumbar spinal fluid. Na¹³¹I dynamics may serve as a model for other molecules actively transported out of cerebrospinal fluid, such as 5-hydroxy-indoleacetic acid; descent into caudal spinal fluid may depend on the degree of efflux from cerebrospinal fluid and on the animal's activity.     

Development of Sustained Release Capsules Containing “Coated Matrix Granules of Metoprolol Tartrate”

The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer–Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R² = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.Key words: biopharmaceutical evaluation, coated granules, metoprolol tartrate, sustained release     

Rheological Characterization and Drug Release Studies of Gum Exudates of Terminalia catappa Linn

The present study was undertaken to evaluate the gum exudates of Terminalia catappa Linn. (TC gum) as a release retarding excipient in oral controlled drug delivery system. The rheological properties of TC gum were studied and different formulation techniques were used to evaluate the comparative drug release characteristics. The viscosity was found to be dependent on concentration and pH. Temperature up to 60°C did not show significant effect on viscosity. The rheological kinetics evaluated by power law, revealed the shear thinning behavior of the TC gum dispersion in water. Matrix tablets of TC gum were prepared with the model drug dextromethorphan hydrobromide (DH) by direct compression, wet granulation and solid dispersion techniques. The dissolution profiles of the matrix tablets were compared with the pure drug containing capsules using the USP Basket apparatus with 500 ml phosphate buffer of pH 6.8 as a dissolution medium. The drug release from the compressed tablets containing TC gum was comparatively sustained than pure drug containing capsules. Even though all the formulation techniques showed reduction of dissolution rate, aqueous wet granulation showed the maximum sustained release of more than 8 h. The release kinetics estimated by the power law revealed that the drug release mechanism involved in the dextromethorphan matrix is anomalous transport as indicated by the release exponent n values. Thus the study confirmed that the TC gum might be used in the controlled drug delivery system as a release-retarding polymer.     

Failure of Cytochalasin or Colchicine to inhibit Secretion of Immunoglobulins

SECRETIONS are often packaged in granules which are held within the cells of origin until some specific stimulus brings about release by exocytosis. Granules containing catecholamines are liberated from adrenal medullary cells by acetylcholine; granules containing insulin are released from pancreatic β-cells by high concentrations of glucose; and granules containing histamine, serotonin and slow-reacting substance are discharged from mast cells in the presence of cell-bound antibody and antigen. The release of secretory granules requires calcium ions in the extracellular medium¹ and may follow the entry into the cytoplasm of calcium ions which trigger contraction of an actomyosin-like microfilament system². This interpretation is supported by our recent observation² that induced release from mast cells of granules containing mediators of acute hypersensitivity is strongly inhibited by cytochalasins, a group of fungal products that selectively block the activity of microfilament-related contractile systems in many cells^3,4. Stimulated release of ¹³¹I from previously labelled mouse thyroids and endocytosis of colloid, are also inhibited by cytochalasin⁵. Cytochalasin inhibits cell movement, movement of ruffled membranes, pinocytosis and phagocytosis in macrophages and polymorphonuclear leucocytes^4,6. Release of ¹³¹ I from previously ¹³¹I-labelled mouse thyroid⁷ is also inhibited by colchicine and other agents that disperse labile cytoplasmic microtubules. Thus it seems that a contractile microfilament-related system, acting together with microtubules, brings about the controlled release, when required, of certain secretions.     

Intragastric floating drug delivery system of cefuroxime axetil: In vitro evaluation

This investigation describes the development of an intragastric drug-delivery system for cefuroxime axetil. The 3² full factorial design was employed to evaluate contribution of hydroxypropyl methyl cellulose (HPMC) K4M/HPMC K100 LV ratio (polymer blend) and sodium lauryl sulfate (SLS) on drug release from HPMC matrices. Tablets were prepared using direct compression technique. Formulations were evaluated for in vitro buoyancy and drug release study using United States Pharmacopeia (USP) 24 paddletype dissolution apparatus using 0.1N HCl as a dissolution medium. Multiple regression analysis was performed for factorial design batches to evaluate the response. All formulations had floating lag times below 2 minutes and constantly floated on dissolution medium for more than 8 hours. It was found that polymer blend and SLS significantly affect the time required for 50% of drug release, percentage drug release at 12 hours, release rate constant, and diffusion exponent (P<.05). Also linear relationships were obtained between the amount of HPMC K100 LV and diffusion exponent as well as release rate constant. Kinetic treatment to dissolution profiles revealed drug release ranges from anomalous transport to case 1 transport, which was mainly dependent on both the independent variables. Published: February 24, 2006     

The Influence of Simulated Fasted Gastrointestinal pH Profiles on Diclofenac Sodium Dissolution in a Glass-Bead Flow-Through System

High inter- and intra-individual variability in the pH of fluids in the human gastrointestinal (GI) tract has been described in the literature. The aim of this study was to assess the influence of physiological variability in fasted pH profiles of media along the GI tract on diclofenac sodium (DF-Na) dissolution from matrix tablets. Four individual in vivo fasted pH profiles were selected from the literature that differed in pH values and transit times from the stomach to the proximal colon. Using a glass-bead device flow-through dissolution system, these pH profiles were simulated in vitro using a specific media sequence and considering simulated intestinal buffer capacities corresponding to in vivo literature data. Dissolution experiments were then performed in the same system with media sequence following individual pH profiles. In dissolution experiments, where influences of simulated gastric emptying time (GET), gastric pH value, small intestinal transit time, and colonic pH were studied; high influence of gastric pH value and GET on DF-Na dissolution was observed. The effect of variability in pH profiles in the range of individual in vivo data on DF-Na dissolution was also clearly observed in experiments, where dissolution studies were performed following three simulated in vivo individual pH profiles. The differences in DF-Na release between three individual pH profiles were substantial; they also reflected in simulated plasma concentration profiles and can be attributed to pH dependent diclofenac solubility.     

Discussion on radioactive iodine treatment of hyperthyroidism and the risk of induced cancer

Iodine-131 (¹³¹I, radioiodine) has been used for over eight decades for the treatment of Graves’ disease, either as initial therapy or following failure of thionamides, as well as for the treatment of autonomous thyroid nodules. ¹³¹I treatment is simple to administer, effective, and relatively inexpensive. Recently, there has been some turmoil after a study published in JAMA Internal Medicine reported an increased risk of cancer from ¹³¹I treatment. The impact was of short duration however, as the paper received severe criticisms from many nuclear medicine physicians as well as from endocrinologists. Here we explain why that paper's conclusions are doubtful. We also review the major data on the topic of ¹³¹I therapy of hyperthyroidism and the risk of cancer.     

Studying the phosphorus release from the Loosdrecht Lakes sediments,using a continuous flow system

Phosphorus release from the Loosdrecht Lakes sediments was studied, using a continuous flow reactor. The summer release maxima were 4 mg P.m^–2.d^–1 in 1984 and 1.4 mg P.m^–2.d^–1 in 1985. Temperature and downward seepage controlled release rates to a great extent, the pH of the overlying water being only of minor importance. From these results it could be concluded that release processes might be driven by mineralization of particulate organic phosphorus in the sediment. Pore water studies in the sediments of the release reactor confirmed this hypothesis. From the profiles phosphorus dissolution rates were calculated.     

Analysis of polypeptide disposition in human erythrocyte membranes employing membrane inversion

High resolution segregation of erythrocyte membrane polypeptides achieved by isoelectric focusing in 8 M urea was employed in conjunction with surface-restricted radioiodination to analyze the disposition of polypeptides within the human erythrocyte membrane. Several membrane polypeptides showed significant uptake of radioiodine, with the principal labeled component migrating between pH values of 3.0 and 3.5. Two approaches were taken in examining membrane polypeptide disposition on both faces of the erythrocyte membrane. Saturation labeling of the outer face of the membrane with one iodine isotope followed by cell lysis and re-iodination with a second iodine isotope did not prove feasible and another procedure based on surface iodination with ¹²⁵I, formation of sealed inside-out vesicles and re-iodination with ¹³¹I was adopted. Studies of sialic acid release from the membrane surface and trypsin cleavage of radioiodinated peptides indicated that selectively labeled, sealed inside-out vesicles had been formed. The ratio of ¹²⁵I to ¹³¹I in membrane polypeptides separated by isoelectric focusing confirmed the existence of externally disposed, internally disposed and spanning proteins.     

NLR、PLR与分化型甲状腺癌术后131I清甲效果的关系及其预测价值分析

摘要 目的：探讨中性粒细胞/淋巴细胞比值（NLR）、血小板/淋巴细胞比值（PLR）与分化型甲状腺癌（DTC）术后碘131（¹³¹I）清甲治疗效果的关系及对DTC术后¹³¹I清甲效果的预测价值。方法：选择2019年3月至2021年12月在江苏大学附属徐州医院行甲状腺切除术且术后进行¹³¹I清甲治疗的DTC患者150例为研究对象,根据¹³¹I清甲治疗效果分为清甲成功组（107例）和清甲未成功组（43例）,通过检查血常规获得中性粒细胞计数、血小板计数、淋巴细胞计数并计算NLR、PLR,比较两组NLR、PLR;采用单因素及多因素logistics回归模型分析¹³¹I清甲疗效的影响因素,采用受试者工作特征曲线（ROC）分析NLR、PLR对¹³¹I清甲治疗效果的预测价值。结果：清甲成功组NLR、PLR低于清甲未成功组（P＜0.05）,单因素分析显示清甲成功组促甲状腺激素（TSH）高于清甲未成功组,甲状腺球蛋白（Tg）水平低于清甲未成功组,清甲成功组病灶最大径小于清甲未成功组（P＜0.05）;多因素logistics回归分析显示,高NLR、PLR、Tg是¹³¹I清甲治疗失败的独立危险因素（P＜0.05）;NLR、PLR及联合检测预测¹³¹I清甲治疗效果的ROC曲线下面积（AUC）分别为0.760、0.732、0.829,NLR与PLR联合检测的AUC高于二者单独检测。结论：高NLR、PLR是DTC术后¹³¹I清甲未成功的独立危险因素,早期检测NLR、PLR对DTC术后¹³¹I清甲治疗效果具有较好的预测价值。     

Thyroid doses in Ukraine due to 131I intake after the Chornobyl accident. Report II: dose estimates for the Ukrainian population

This paper describes the revision of the thyroid dosimetry system in Ukraine using new, recently available data on (i) revised ¹³¹I thyroid activities derived from direct thyroid measurements done in May and June 1986 in 146,425 individuals; (ii) revised estimates of ¹³¹I ground deposition density in each Ukrainian settlement; and (iii) estimates of age- and gender-specific thyroid masses for the Ukrainian population. The revised dosimetry system estimates the thyroid doses for the residents of the settlements divided into three levels depending on the availability of measurements of ¹³¹I thyroid activity among their residents. Thyroid doses due to ¹³¹I intake were estimated in this study for different age and gender groups of residents of 30,353 settlements in 24 oblasts of Ukraine, Autonomous Republic Krym, and cities of Kyiv and Sevastopol. Among them, dose estimates for 835 settlements were based on ¹³¹I thyroid activities measured in more than ten residents (the first level), for 690 settlements based on such measurements done in neighboring settlements (the second level), and for 28,828 settlements based on a purely empirical relationship between the thyroid doses due to ¹³¹I intake and the cumulative ¹³¹I ground deposition densities in settlements (the third level). The arithmetic mean of the thyroid doses due to ¹³¹I intake among 146,425 measured individuals was 0.23 Gy (median of 0.094 Gy); about 99.8% of them received doses less than 5 Gy. The highest oblast-average population-weighted thyroid doses were estimated for residents of Chernihiv (0.15 Gy for arithmetic mean and 0.060 Gy for geometric mean), Kyiv (0.13 and 0.051 Gy) and Zhytomyr (0.12 and 0.049 Gy) Oblasts followed by Rivne (0.10 and 0.039 Gy) and Cherkasy (0.088 and 0.032 Gy) Oblasts, and Kyiv City (0.076 and 0.031 Gy). The geometric mean of thyroid doses estimated in this study for the entire Ukraine essentially did not change in comparison with a previous estimate, 0.020 vs. 0.021 Gy, respectively. The ratio of geometric mean of oblast-specific thyroid doses estimated in the present study to previously calculated doses varied from 0.51 to 3.9. The highest increase in thyroid doses was found in areas remote from the Chornobyl nuclear power plant with a low level of radioactive contamination: by 3.9 times for Zakarpatska Oblast, 3.5 times for Luhansk Oblasts and 2.9 times for Ivano-Frankivsk Oblast. The developed thyroid dosimetry system is being used to revise the thyroid doses due to ¹³¹I intake for the individuals of post-Chornobyl radiation epidemiological studies: the Ukrainian-American cohort of individuals exposed during childhood and adolescence, the Ukrainian in utero cohort, and the Chornobyl Tissue Bank.

     

Enzymes in the Dissolution Testing of Gelatin Capsules

Gelatin capsules are a widely used dosage form both for pharmaceutical drug products as well as dietary supplements. Gelatin in the presence of certain compounds, mainly aldehydes, or in high humidity and high temperature conditions can cross-link. Cross-linking involves covalent bonding of the amine group of a lysine side chain of one gelatin molecule to a similar amine group on another molecule. The covalent bonding is, for practical purposes, irreversible. Cross-linking results in the formation of a pellicle on the internal or external surface of the gelatin capsule shell that prevents the capsule fill from being released. In vitro dissolution testing of cross-linked gelatin capsules can result in slower release of the drug or no release at all. The data obtained by the Gelatin Capsule Working Group, created in the early 90s to investigate noncompliance of gelatin capsules, was used to establish the type and amounts of enzymes that can be added to the dissolution medium in the case of test failure to the presence of cross-linking in the gelatin. The two-tier dissolution testing was included in the US Pharmacopeia and it recommends the addition of pepsin (pH below 6.8) or pancreatin (pH above 6.8) to the medium depending on its pH. Pepsin shows good protease activity up to pH 4 and pancreatin above pH 6 leaving a gap where neither one has good activity. Possible proteolytic enzymes that could be used for the pH range 4–6.8 could be papain or bromelain.KEY WORDS: cross linking, gelatin capsules, two-tier dissolution testing     

A Case of Esophageal Stricture After Iodine 131 Ablation

ObjectiveTo report the first case of esophageal stricture as a complication of radioiodine (¹³¹I) ablation therapy.MethodsWe review the medical and surgical history of this patient and discuss various potential causes of the esophageal stricture.ResultsA 79-year-old woman presented with increasing dysphagia and weight loss of about 4.5 kg after recent ¹³¹I therapy for thyroid cancer remnant ablation. Her pertinent history included gastroesophageal reflux disease, an anterior midcervical esophageal web, and a distal esophageal stricture. She also had a history of radiation therapy to her chest for breast cancer about 28 years previously. On the day of ¹³¹I therapy, the 5.5-GBq ¹³¹I capsule lodged accidentally in her midcervical area for approximately 2.5 hours. The resulting radiation dose to the proximal esophagus was estimated to be 7.86 Gy from gamma radiation and possibly as high as several thousand grays from beta radiation. During this time, the esophagus had possible direct exposure to the sodium phosphate dibasic that was used as filler in the sodium iodide capsule. Because of the worsening dysphagia, an esophagogastroduodenoscopy was performed 4 weeks after the ¹³¹I therapy, which showed a new proximal esophageal stricture.ConclusionWe believe that the additional localized radiation and sodium phosphate exposure from the lodging of the ¹³¹I capsule may have contributed to the development of a proximal esophageal stricture. To our knowledge, such an occurrence has not previously been described in the medical literature. For prevention of such an occurrence, we recommend a careful swallowing evaluation of patients with any history of esophageal radiation exposure, dysphagia, or esophageal strictures before administration of ¹³¹I in capsule form. Alternative methods of ¹³¹I delivery, if available, should be considered. (Endocr Pract. 2012;18: e61-e64)     

Investigating the Dissolution Profiles of Amoxicillin,Metronidazole, and Zidovudine Formulations used in Trinidad and Tobago,West Indies

Trinidad and Tobago is a twin-island Republic in the Caribbean and like many developing countries, it has included generic drugs on the national drug formulary to decrease the financial burden of pharmaceutical medications. However, to ensure that medications received by patients are beneficial, generic drugs need to be interchangeable with the innovator which has demonstrated safety, efficacy, and quality. The objective of the study was to compare the dissolution profiles and weight variations for different formulations of amoxicillin, metronidazole, and zidovudine that are on the national drug formulary and marketed in Trinidad and Tobago. All the products investigated are categorized as class 1 drugs according to the Biopharmaceutics Classification System (BCS) and the dissolution profiles were assessed according to the World Health Organization (WHO) criteria for interchangeability between products. The similarity factor, f₂, was used to determine sameness between the products. No generic formulation was found to be similar to Amoxil® 500-mg capsules. The two generic products for metronidazole 200-mg tablets demonstrated more than 85% drug release within 15 min in all three of the buffers; however, their 400-mg counterparts did not fulfill this requirement. The zidovudine 300-mg tablet complied with the requirements in buffer pH 4.5 and simulated gastric fluid (SGF) but not for simulated intestinal fluid (SIF). Some Class 1 pharmaceutical formulations may possess the same active ingredient and amount of drug but may show significant differences to in vitro equivalence requirements. Nevertheless, the dissolution process is suitable to detect these variations.KEY WORDS: biopharmaceutics classification system, dissolution, generic drugs, interchangeability, in vitro equivalence     

Radioactive Iodine Therapy Without Recent Antithyroid Drug Pretreatment For Hyperthyroidism Complicated By Severe Hyperbilirubinemia Due To Hepatic Dysfunction: Experience Of A Chinese Medical Center

Objective: The objective of this work is to report our experience with ¹³¹I therapy without recent antithyroid drug (ATD) pretreatment for refractory severe hyperthyroidism complicated by hyperbilirubinemia due to hepatic dysfunction.Methods: Five patients with refractory severe hyperthyroidism were treated with ¹³¹I at 90 to 120 μCi/g-thyroid (total activity, 6.2 to 10.1 mCi). The patients previously had received ATD treatment from 2 months to 12 years and discontinued ATDs from 2 months to 4 years before ¹³¹I treatment due to treatment failure or severe jaundice. Prior to ¹³¹I therapy, the patients were asked to take a low-iodine diet and were treated with bisoprolol fumarate, digoxin, furosemide, S-adenosylmethionine, polyene phosphatidylcholine, and plasma exchange as supportive treatment for related clinical conditions. Four of the patients also received lithium carbonate in conjunction with their ¹³¹I treatment. The patients were followed for 4 to 9 years after ¹³¹I therapy.Results: After ¹³¹I treatment, jaundice disappeared completely within 3 to 4 months in all patients, and liver function tests returned to normal. Concurrent atrial fibrillation and heart failure, leukopenia and thrombocytopenia, or thrombocytopenia and left cardiac enlargement improved remarkably in 3 patients during the follow-up period. Three to 45 months after ¹³¹I treatment, hypothyroidism was noted in the patients and they were treated with L-thyroxine replacement therapy.Conclusion:¹³¹I therapy without recent ATD pretreatment for refractory severe hyperthyroidism complicated by serious jaundice appears to be safe and effective, with good long-term results. It may be the preferred therapy for such patients and should be used as early as possible.Abbreviations:ATD = antithyroid drugFT₄ = free thyroxinePTU = propylthiouracilRAIU = radioactive iodine uptakeTSH = thyroid-stimulating hormone     

Intrathyroidal iodine metabolism in the rat. The influence of diet and the administration of thyroid-stimulating hormone

1. Ratios of mono[¹³¹I]iodotyrosine and di[¹³¹I]iodotyrosine (R values) and the incorporation of ¹³¹I into iodothyronines have been estimated in rat thyroid glands from 30min. to 38hr. after the administration of [¹³¹I]iodide. 2. In rats receiving a powdered low-iodine diet the R values were close to unity and did not change with time after the administration of [¹³¹I]iodide. In rats receiving a commercial pellet diet the R values fell from a mean of 0·8 at 30min. after [¹³¹I]iodide administration to 0·49 at 38hr. 3. Administration of 0·5–2·0i.u. of thyroid-stimulating hormone before giving the injection of [¹³¹I]iodide caused a small diminution in the R value when the time between injecting [¹³¹I]iodide and killing the animal was 16hr. or more. 4. Iodothyronines represented a greater percentage of the total thyroid-gland radioactivity in the iodine-deficient animals than in animals fed on the pellet diet. Thyroid-stimulating hormone had little effect, if any, on the iodothyronine contents.