Steroid profile and IRMS analysis of musk administration for doping control.

Musk, the dried secretion of the musk pod (sac) of adult male musk deer, has been used as traditional Chinese Medicine (TCM) in China and south-east Asian countries for thousands of years. Due to the anabolic steroid component in this TCM, musk preparations have been included in the list of medical products containing prohibited substances employed for doping by the State Food and Drug Administration of China. The application of musk pod formulation was claimed to be responsible for some adverse analytical findings (AAFs) in the 2011 FIFA Women's World Cup. Our preliminary study has suggested that musk ingestion did not lead to AAFs of doping control with the single dosage of 100 mg. However, the influences of musk administration in large and multi dosage are still unclear. The aim of this study is to further investigate the influences of musk administration for doping control. Wild and domestic deer musk samples were collected. The concentrations and δ13 C-values of steroids in musk were analyzed. In an excretion study, 200 and 100 mg of wild and domestic deer musk samples were administrated by 29 subjects, respectively. Fluctuations in steroid profile could be observed, and the ratio of 5α-androstane-3α,17ß-diol to 5ß-androstane-3α,17ß-diol was more sensitive than other parameters. In the IRMS test, the ∆Δδ13 C-value between endogenous reference compound and etiocholanolone was a sensitive parameter, and AAFs were obtained. It is the first time to confirm with excretion study that musk administration could lead to positive result of doping control. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of 3α-anderostanediol and indomethacin on acquisition, consolidation and retrieval stage of spatial memory in adult male rats.

BACKGROUND: Testosterone and its metabolites have important roles in learning and memory. The current study has conducted to assess the effect of pre-training, post-training and pre-probe trial intrahippocampal CA1 administration of 3α-anderostanediol (one of the metabolites of testosterone) and indomethacin (as 3α-hydroxysteroid dehydrogenase enzyme blocker) on acquisition, consolidation and retrieval in Morris water maze (MWM) task. METHODS: Adult male rats were bilaterally cannulated into CA1 region of hippocampus and then received 3α-diol (0.2, 1, 3 and 6 mug/0.5 mul/side), indomethacin (1.5, 3 and 6 mug/0.5 mul/side), indomethacin (3 mug/0.5 mul/side) + 3α-diol (1 mug/0.5 mul/side), 25-35 min before training, immediately after training and 25-35 min before probe trial in MWM task. RESULTS: Our results showed that injection of 3α-diol and indomethacin significantly increased the escape latency and traveled distance to find hidden platform in acquisition and consolidation stage, but did not have any effect on retrieval of spatial learning as compared with the control group. CONCLUSION: It is concluded that intra-CA1 administration of 3α-diol and indomethacin could impair spatial learning and memory in acquisition and consolidation stage. Also, intrahippocampal injection of indomethacin + 3α-diol could not change spatial learning and memory impairment effect of indomethacin or 3α-diol in MWM task.

Activation of NK1 receptors in the locus coeruleus induces analgesia through noradrenergic-mediated descending inhibition in a rat model of neuropathic pain.

BACKGROUND AND PURPOSE: The locus coeruleus (LC) is a major source of noradrenergic projections to the dorsal spinal cord, and thereby plays an important role in the modulation of nociceptive information. The LC receives inputs from substance P (SP)-containing fibres from other regions, and expresses the NK(1) tachykinin receptor, a functional receptor for SP. In the present study, we investigated the roles of SP in the LC in neuropathic pain. EXPERIMENTAL APPROACH: Chronic constriction injury (CCI) of the left sciatic nerve was performed in rats to induce neuropathic pain. After development of neuropathic pain, SP was injected into the LC and the nocifensive behaviours were assessed. The involvement of noradrenergic descending inhibition in SP-induced analgesia was examined by i.t. administration of yohimbine, an α(2) -adrenoceptor antagonist. NK(1) receptor expression in the LC was examined by immunohistochemistry. KEY RESULTS: In CCI rats, mechanical allodynia was alleviated by SP injection into the LC. These effects were abolished by prior injection of WIN 51708, an NK(1) receptor antagonist, into the LC or i.t. treatment with yohimbine. NK(1) receptor-like immunoreactivity was observed in noradrenergic neurons throughout the LC in intact rats, and remained unchanged after CCI. CONCLUSION AND IMPLICATIONS: SP in the LC exerted analgesic effects on neuropathic pain through NK(1) receptor activation and resulted in facilitation of spinal noradrenergic transmission. Accordingly, manipulation of the SP/NK(1) receptor signalling pathway in the LC may be a promising strategy for effective treatment of neuropathic pain.

Intra-articular administration of tachykinin NK1 receptor antagonists reduces hyperalgesia and cartilage destruction in the inflammatory joint in rats with adjuvant-induced arthritis.

Persistent pain associated with inflammatory arthritis is an aggravating factor that decreases patients' quality of life. Current therapies for joint pain have limited effectiveness and produce unwanted negative side effects. Although the involvement of substance P and its cognate tachykinin receptor, NK(1), in joint inflammation has been extensively documented through animal experiments, the development of oral tachykinin NK(1) receptor antagonists against arthritis-induced pain has been unsuccessful in humans to date. To explore the possibility of using tachykinin NK(1) receptor antagonists as local therapeutic agents for inflammatory arthritis, we examined the effects of tachykinin NK(1) receptor antagonists administered into the rat ankle joint on hyperalgesia in complete Freund's adjuvant (CFA)-induced inflammatory monoarthritis. Administration of the tachykinin NK(1) receptor antagonist WIN 51708 or GR 82334 into the affected ankle joint at day 3 following intra-articular CFA injection reduced the mechanical hyperalgesia 12 h after the tachykinin NK(1) receptor antagonist injection and their analgesic effects persisted for at least 2 days. Histological examinations revealed that intra-articular WIN 51708 reduced the CFA-induced destructive changes in the cartilage. These findings suggest that intra-articular injection of tachykinin NK(1) receptor antagonists is a promising strategy for relieving the hyperalgesia that occurs in inflammatory arthritis.

[Ultrasonographic histological study on the evolution of a canine model of hormone-induced benign prostatic hyperplasia]. / Estudio ultrasonográfico e histológico de la evolución de un modelo canino de hiperplasia benigna de próstata inducida por hormonas.

INTRODUCTION: Despite exhibiting histological differences from the human process, canine hormone-induced benign prostatic hyperplasia (BPH) is still the most widely used animal model for evaluating treatment strategies. OBJECTIVES: The aim of this study is to determine the optimal moment for starting a therapeutic trial in this animal model. MATERIAL AND METHODS: Six male beagle dogs over one year of age were used in this study. All animals received a combination of steroid hormones, namely 17beta-estradiol and 5alpha-androstene 3alpha 17beta-diol, every other day during three (Group 1, n=3) or five months (Group 2, n=3). Transrectal ultrasonographic examinations to measure prostate volume were performed monthly. Animals were euthanized after five months for histological study of their prostates. RESULTS: All animals developed BPH, with prostate volume increasing over time as hormones were administered (r=0,910). All ultrasonographic studies performed up to the third month evidenced a significant increase in prostate volume when compared to the prior ultrasound measurement. A significant decrease in prostate volume was seen in Group 1 once hormone administration was interrupted, whereas Group 2 animals showed a continuing increase in prostate size. Histological examination showed almost no evidence of BPH in Group 1 animals, while Group 2 animals clearly exhibited moderate epithelial hyperplasia. CONCLUSIONS: The administration of a combination of steroid hormones is effective in inducing benign prostatic hyperplasia in canines, but this hyperplasia disappears when hormone treatment is interrupted. In order to be useful for experimental studies, hormones should be administered for at least three months before commencing any treatment, and they should be continued throughout the length of the study..

In vivo activity of anprocide alone, and in vitro activity in combination with conventional antibiotics against Staphylococcus aureus and Staphylococcus epidermidis biofilms.

The alarming spread of multiple drug resistance in Staphylococcus aureus, combined with the frequent occurrence of S. aureus and Staphylococcus epidermidis in biofilm-type infections, indicates a growing need for new therapies. The experimental steroidal amide anprocide [3beta-acetoxy-17beta-(l-prolyl)amino-5alpha-androstane] significantly reduced c.f.u. ml(-1) per suture (P <0.0001) in a murine model of topical S. aureus infection. In chequerboard assays with planktonic-grown S. aureus and S. epidermidis, anprocide was synergistic with bacitracin, oxacillin, clindamycin or ceftriaxone. Anprocide was also synergistic in combination with bacitracin or oxacillin against some isolates of biofilm-grown S. aureus and S. epidermidis.

Effects of substance P microinjections into the globus pallidus and central nucleus of amygdala on passive avoidance learning in rats.

Substance P (SP) has been implicated in learning and memory processes. This peptide facilitated learning when injected peripherally or directly into the ventral pallidum. SP has high affinity for neurokinin-1 (NK-1) receptors. WIN51,708 is a potent NK-1 receptor antagonist that can inhibit the physiological effects of SP. Immunohistochemical experiments showed that the globus pallidus (GP) and the amygdaloid (AMY) body are rich in SP immunoreactive elements. Pallidal lesions cause learning deficits in active and passive avoidance paradigms. Serious memory deficits develop after lesions of AMY and its role in conditioned fear has been suggested. The aim of our study was to examine whether the SP microinjected into the GP or central nucleus of AMY (ACE) can modify negative reinforcement. Male Wistar rats were conditioned in a passive avoidance situation. Animals were microinjected with 0.4 microl of 10 ng SP, 100 ng SP or vehicle solution into the GP or the ACE. Results showed that 10 ng SP significantly enhanced passive avoidance learning in both structures, while 100 ng SP was ineffective. Retention examined 1 week later was diminished in the GP and still significant in the ACE. The possible involvement o NK-1 receptors in the effects of SP microinjected into the ACE was also studied. Prior treatment with WIN51,708 could block the SP effects on passive avoidance paradigm. Our results are the first to demonstrate that SP plays important roles, though in different ways, in learning and memory processes related to the GP and AMY.

Effect of cholesterol and ethanol on dermal delivery from DPPC liposomes.

The main objective of the present work was to compare the dermal delivery of minoxidil (Mx), a lipophilic drug from ethosomes versus classic liposomes, containing different cholesterol (CHOL) concentrations. All the systems were characterized for shape, lamellarity, particle size and entrapment efficiency percentage (EE), by transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), laser diffraction and ultracentrifugation or dialysis methods, respectively. Multilamellar vesicles (MLVs) were obtained and one to six lamellae were visualized by CLSM. The presence of ethanol in the formulations affects the particle size in terms of reducing this parameter. In addition, it was possible to appreciate the influence of CHOL on the vesicle size, because it was increased, as CHOL concentration was higher. When the EE was determined by two different methods (ultracentrifugation and dialysis methods), a clear losing of entrapped drug by the ultracentrifugation method was observed, because the strong energy transmitted to the samples disrupted vesicles. Vesicles were non-occlusively applied on rat skin and the permeation pattern of the different systems, depth into the skin and the main permeation pathway were studied by using beta-carotene as a fluorescent probe. CLSM studies showed that ethosomal systems were much more efficient at delivering the fluorescent substance into the skin in terms of quantity and depth, than either liposomes or hydroalcoholic solutions.

A new short-acting non-depolarizing muscle relaxant (SZ1677) without cardiovascular side-effects.

BACKGROUND: In order to facilitate rapid tracheal intubation, the development of a rapid onset, short duration, non-depolarizing muscle relaxant without cardiovascular side-effects would be a significant accomplishment in the field of anesthesiology. The aim of the present study was to test the action of a new non-depolarizing muscle relaxant (SZ1677) on neuromuscular transmission, muscarinic (M2, M3) receptors and cardiovascular reactions and to compare it with clinically used muscle relaxants. METHODS: Neuromuscular transmission was studied by recording muscle contractions elicited by indirect electrical stimulation, using (i). in vitro isolated phrenic nerve-hemidiaphragm preparation of mice, rats and guinea pigs and (ii). in vivo sciatic nerve-anterior tibial muscle preparation of anesthetized rats, guinea pigs and cats. Cardiovascular effects of muscle relaxants were evaluated on the grounds of their effects on changes of blood pressure and heart rate induced by electrical stimulation of the right vagal nerve in anesthetized cats. To study postsynaptic antimuscarinic affinity of muscle relaxants on M3 receptors, oxotremorine-induced contractions of longitudinal muscle strip of guinea pig ileum were registered in their presence and absence. RESULTS: One of more than 120 newly synthesized non-depolarizing muscle relaxants compounds, 1-3[alpha-hydroxy-17beta-acetyloxy-2beta-(1,4-dioxa-8-azaspiro[4,5]dec-8-yl)-5alpha-androstane-16beta-il] -1-(2-propenyl)pyrrolidinium bromide (SZ1677), excelled with its advantageous pharmacological properties: relatively short duration of action, no accumulation and lack of unwanted side-effects. Pharmacodynamic studies show that SZ1677 is a non-depolarizing neuromuscular blocking agent with a relatively short duration and rapid onset of action in a variety of laboratory animal species. It is without cumulative effect, does not reduce blood pressure, and fails to produce tachycardia. Significant cardiac vagal blocking effects were not observed even at concentrations or dosages of 8 times the ED90. This compound, unlike many other muscle relaxants, does not have atropine-like effects on human atrial tissue; it does not increase the release of NA from sympathetic innervation in the heart. In all practical ways, at least from the vantage point of the preclinical study, SZ1677 compares favorably with all presently available short-acting muscle relaxants, including rapacuronium. CONCLUSION: In experiments, SZ1677 proved to be a short-acting neuromuscular blocking compound having a large safety margin between the doses required to produce neuromuscular block and those likely to lead to cardiovascular side-effects.

A new agglomerated KSR-592 beta-form crystal system for dry powder inhalation formulation to improve inhalation performance in vitro and in vivo.

A new agglomerated KSR-592 (steroid) beta-form needle-like crystals with lactose system for dry powder inhalation (DPI) was developed to improve inhalation performance with Jethaler. The drug agglomerates were prepared by the method of spherical agglomeration in liquid so as to control the particle size and the mechanical strength of agglomerates by changing the agitation speed of the agglomeration system. The agglomerates mixed with lactose particles for the DPI formulation were effectively disintegrated into respirable fine particle in the milling chamber of the device (Jethaler) when inhaled. The DPI formulation with these agglomerates exhibited ideal fluidity and provided a larger fine particle fraction (FPF: 29.7%) than the formulation with agglomerates consisting of alpha-form (plate-like) crystals (24.5%). The air-flow rate of inhalation had no effect on the disintegration properties of these agglomerates, suggesting a reliable inhalation performance in vivo. Further, an in vivo test of the aerosolized KSR-592 (beta-form) crystals having the same particle size distribution as those in the aerosol produced by Jethaler was conducted by means of a dry powder inhalation testing system using Brown Norway rats. Inhaled KSR-592 (beta-form) crystals were found to be uniformly deposited in the lungs of Brown Norway rat sensitized by ovalbumin (OA) and suppressed the increase in eosinophil number in the lungs after OA challenge.

Improved inhalation behavior of steroid KSR-592 in vitro with Jethaler by polymorphic transformation to needle-like crystals (beta-form).

PURPOSE: The aim of the present study was to improve the dry powder inhalation behavior of steroid KSR-592 with lactose by altering the crystal shape and the particle size of the drug for use in a newly designed inhalation device, Jethaler. METHOD: The shape of the crystals was changed by polymorphic transformation of original crystal (alpha-form) to beta-form by agitating alpha-form crystals in hexane containing 5% ethanol. The inhalation properties of the resultant crystals in vitro were evaluated with a twin impinger and cascade impactor. RESULTS: Needle-like crystals (beta-form) with dimensions of 1.8 microm in width x 41 microm in length were obtained by the polymorphic transformation, the kinetics of which was described by the Avrami equation. The beta-form crystals loaded on lactose particles were easily separated and crushed into fine particles in the airstream produced in the Jethaler, which increased dramatically the respirable fraction (RF) deposited in the twin impinger (43.8%) and the fine particle fraction (FPF) of the cascade impactor (FPF = 39.3%) compared with their values for the original crystals (RF = 5.8%, FPF = 4.7%). CONCLUSION: The dry powder inhalation properties of steroid KSR-592 (platelike crystal, alpha-form) were improved dramatically by changing the crystal shape to a needle-like shape by the polymorphic transformation to the beta-form.

Place aversion induced by microinjections of C-fragment of substance P into the dorsal periaqueductal gray of rats is mediated by tachykinin NK1 receptors.

Neural circuits in the dorsal periaqueductal gray matter (dPAG) play an important role in the integration of defensive behavior. The neurokinin substance P causes conditioned place aversion when administered into this region. The present study examined whether these effects may be mimicked by its carboxy-terminal amino acid sequence and whether they are influenced by prior treatment with the tachykinin NK1 receptor antagonist WIN51,708. The behavioral testing apparatus is a circular open field consisting of 4 uniform quadrants that are equally preferred by the rats prior to drug treatments. For conditioning, rats received drug injections on three consecutive days and were placed into their assigned quadrant. The carboxy-terminal analog (17.5 pmol/0.2 microl) applied into the dPAG produced place aversion effects with reduced time spent in the drug-paired quadrant on the testing day. The effects of the carboxy-terminal analog was antagonized by pretreatment with WIN51,708 (20 mg/kg, i.p.). Microinjection of WIN51,708 (20 mg/kg, i.p.), by its own, did not produce significant effects. These findings suggest that previous reports showing conditioned place aversion effects of SP injected into the dPAG are encoded by its carboxy-terminal sequence and due to its action on tachykinin NK1 receptors.

Involvement of substance P and central opioid receptors in morphine modulation of the CHS response.

Morphine administration prior to challenge with the antigen 2,4-dinitro-fluorobenzene increases the contact hypersensitivity (CHS) response in rats. The present study extended these findings by showing that central, but not systemic, administration of N-methylnaltrexone antagonized the morphine-induced enhancement of the CHS response. The importance of the neuroimmune mediator substance P was shown via the attenuation of the morphine-induced enhancement following both systemic and topical administration of the NK-1 antagonist WIN51,708. Taken together, the findings of the present study provide new data showing that central opioid receptors and peripheral substance P are involved in the morphine-induced enhancement of the CHS response.

Influência do sevoflurano e do isoflurano na duraçäo do bloqueio neuromuscular produzido pelo rocurônio / Influence of sevoflurane and isoflurane in rocuronium-induced neuromuscular block duration

Justificativa e objetivos: Os efeitos dos agentes bloqueadores neuromusculares sobre a junçäo neuromuscular säo potencializados por anestésicos voláteis, de forma dose dependente. O objetivo deste estudo foi avaliar a influência do sevoflurano e do isoflurano na recuperaçäo do bloqueio neuromuscular produzido pelo rocurônio. Método: foram estudados 60 pacientes, estado físico ASA I e II, submetidos a cirurgias eletivas sob anestesia geral, distribuídos em dois grupos de acordo com o agente volátil empregado: Grupo I (sevoflurano e Grupo II (isoflurano). Todos os pacientes receberam midazolam (0,1 mg.kg elevado a menos 1) por via muscular como medicaçäo pré-anestésica, 30 minutos antes da cirurgia. A induçäo anestésica foi obtida com propofol (2,5 mg.kg elevado a menos 1). Os pacientes foram ventilados com oxigênio a 100 por cento sob máscara até o desaparecimento das quatro respostas à seqüência de quatro estímulos (SQE), quando foram realizadas as manobras de laringoscopia e intubaçäo traqueal. Os agentes voláteis para a manutençäo da anestesia foram introduzidos após a intubaçäo traqueal e empregados nas concentraçöes de 2 por cento e 1 por cento, respectivamente para o sevoflurano e isoflurano, em mistura de O2eN2O a 50 por cento. Doses adicionais de fentanil foram administradas na vigência de sinais clínicos de anestesia superficial. Os pacientes foram ventilados mecanicamente para manter PetCO2 entre 32 e 36 mmHg. Foram medidas as temperaturas corpórea e da pele sobre a regiäo hipotenar do lado monitorizado, que se mantiveram acima de 35 e 32ºC, respectivamente. A funçäo neuromuscular foi monitorizada com aceleromiografia, empregando-se a SQE a cada 15 segundos. Foram avaliados: a duraçäo clínica do bloqueio neuromuscular (T1 25 por cento) e o índice de recuperaçäo (IR=T1 25 - 75 por cento

Effect of neurokinin-I receptor antagonists on the function of 5-HT and noradrenaline neurons.

Substance P antagonists have been proposed to be a new class of antidepressants. The present study aimed to determine the effect of the selective non-peptide rat neurokinin-1 (NK1) receptor antagonists WIN 51,708 and CP-96,345 on the firing activity of rat dorsal raphe serotonin (5-HT) and locus coeruleus noradrenaline (NA) neurons. While WIN51,708 (2mg/kg, i.v.) and CP-96,345 (0.15 mg/kg, i.v.) did not modify the firing activity of 5-HT and NA neurons, both antagonists attenuated the suppressant effect of the alpha2-adrenoceptor agonist clonidine on the firing activity of both types of neurons. In contrast, the responsiveness of 5-HT neurons to the i.v. administration of the 5-HT autoreceptor agonist LSD and the 5-HT1A receptor agonist 8-OH-DPAT remained unchanged. These findings suggest that NK1 receptor antagonists affect markedly the NA system via an attenuation of the function of alpha2-adrenoceptors on the cell body of NA neurons and, consequently, may also modulate 5-HT neurotransmission.

The role of perceptual and structural similarity in cross-adaptation.

Cross-adaptation, the decrease in sensitivity to one odorant following exposure to a different odorant, is affected by odorant similarity, both perceptual and structural, but the precise relationship is obscure. The present series of studies was designed to explore various aspects of perceptual and structural similarity as they relate to cross-adaptation. In Experiment 1, cross-adaptation was assessed between androstenone and five odorants that share a common urinous note with androstenone, but retain unique perceptual characteristics; only the compound judged most perceptually similar to androstenone cross-adapted it. In Experiment 2, odorants both perceptually and structurally similar (androstenone and androstanone) displayed significant, mutual cross-adaptation. Furthermore, magnitude estimates for androstanone were significantly reduced following exposure to 3-methylidene-5 alpha-androstane (3M5A), a structurally similar, perceptually odorless compound. This finding appears to be the first demonstration that an odorless compound can affect, via cross-adaptation, the perception of an odorous compound. Finally, in Experiment 3, significant, asymmetric cross-adaptation was observed between compounds that are perceptually and structurally dissimilar (4-cyclohexylcyclohexanone [4-CHCH] and androstenone). These findings indicate that the role of similarity in cross-adaptation is difficult to quantify and emphasize the numerous odorant characteristics that can affect cross-adaptation.

Effect of the in vivo treatment with the synthetic steroid 17 beta-methoxy-17-methyl-(5 alpha)-1 H'-androstane-(3,2-c) pyrazole (17MM) on the in vitro formation of DHT in the epididymis of the rat.

Adult male Sprague-Dawley rats were injected subcutaneously (s.c.) for 21 days either with the synthetic steroid 17 beta-methoxy-17-methyl-(5 alpha)-1 H'-androstane-(3,2-c) pyrazole (17MM) at two dose levels (0.1 and 1 mg/kg/day) or with the vehicle used to dilute the steroid. At autopsy, caput epididymes and ventral prostates were removed and incubated in vitro. The effect on the 5 alpha-reductase (5 alpha-R) activity was evaluated by measuring the amounts of DHT formed from 14C-testosterone (14C-T) used as the substrate. The in vivo administration of 17MM at the dose of 0.1 mg/kg/day resulted in a significant decrease in the formation of DHT at the level of the epididymis, while there was no effect on the prostate. The dose of 1 mg/kg/day did not induce any modification in the formation of DHT in either organ. The determination of serum LH showed that the treatment with either dose did not alter serum LH titers. These findings suggest that the in vivo treatment with 17MM lowers the in vitro formation of DHT from T at the epididymal, but not at the prostatic level and consequently suggests a selective inhibitory effect of 17MM on the 5 alpha-R present in the epididymis.

Comparative bioavailability of a lipophilic steroid.

17beta-Acetoxy-2alpha-chloro-3-(p-nitrophenoxy)imino-5alpha-androstane (I) is a lipophilic steroid with postimplantive antifertility activity in laboratory animals. The bioavailability of micronized I from solutions and suspensions was compared in four groups of adult female Wistar rats. Each group received varying concentrations of micronized 3H-I (specific activity of 0.38--8.94 muCi/mg) in sesame oil by oral gavage. Samples of whole blood and urine collected following drug administration were assayed for radioactive content. Calculation of the mean area under the blood radioactivity versus time curve, when corrected for the quantity of drug administered, indicated that a substantially larger fraction of the dose was absorbed in the two instances where I was present only in solution. A linear relationship between the amount of I absorbed based on whole blood radioactivity and urinary excretion and the administered dose was found primarily for groups receiving the drug in solution. Preliminary results in humans indicate that 3H-I was absorbed to a much greater extent following oral administration of the drug in sesame oil than when admixed with lactose.