Recently, anthelmintics have showcased versatile therapeutic potential in addressing various diseases, positioning them as promising candidates for drug repurposing. However, challenges such as low bioavailability and a lack of a solid pharmacokinetic basis impede successful repurposing. To overcome these flaws, we aimed to investigate the key pharmacokinetic factors of anthelmintics mainly focusing on the absorption, distribution, and metabolism profiles by employing niclosamide (NIC) as a model drug. The intestinal permeability of NIC is significantly influenced by solubility and doesn\'t function as a substrate for efflux transporters. It showed high plasma protein binding. Also, the metabolism study indicated that NIC would have low metabolic stability by extensively undergoing the intestinal glucuronidation. Additionally, we investigated the CYP-mediated drug-drug interaction potential of NIC in both direct and time-dependent ways. NIC showed strong inhibitory effects on CYP1A2 and CYP2C8 and is not likely to become a time-dependent inhibitor. Our findings could contribute to the identification of essential factors in the pharmacokinetics of anthelmintics, potentially facilitating their repositioning.

BACKGROUND: To report the first case of bull\'s eye maculopathy associated with veterinary niclosamide.
METHODS: A 27-year-old Iranian female presented with a history of reduced vision and photopsia since 3 years, after accidental ingestion of four boluses of veterinary niclosamide. Fundus examination showed atrophy in parafoveal retinal pigmentary epithelium, appearing as bilateral bull\'s-eye maculopathy. Optical coherence tomography revealed disruption of the parafoveal ellipsoid zone and outer retinal thinning, appearing as a flying saucer sign. Electroretinography displayed decreased scotopic and photopic amplitudes with normal waveform in both eyes. The causality score was 4, showing \"possible\" retinopathy due to niclosamide according to Naranjo\'s causality assessment algorithm. Based on clinical and ancillary findings, a diagnosis of niclosamide-induced maculopathy was made.
CONCLUSIONS: Veterinary niclosamide is an anthelmintic drug that in higher doses could be detrimental to the human retina. Awareness about its side effects and appropriate drug labeling could prevent accidental toxicity.

We developed an amorphous solid dispersion (ASD) of the poorly water-soluble molecule niclosamide that achieved a more than two-fold increase in bioavailability. Notably, this niclosamide ASD formulation increased the apparent drug solubility about 60-fold relative to the crystalline material due to the generation of nanoparticles. Niclosamide is a weakly acidic drug, Biopharmaceutics Classification System (BCS) class II, and a poor glass former with low bioavailability in vivo. Hot-melt extrusion is a high-throughput manufacturing method commonly used in the development of ASDs for increasing the apparent solubility and bioavailability of poorly water-soluble compounds. We utilized the polymer poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP-VA) to manufacture niclosamide ASDs by extrusion. Samples were analyzed based on their microscopic and macroscopic behavior and their intermolecular interactions, using differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), and dynamic light scattering (DLS). The niclosamide ASD generated nanoparticles with a mean particle size of about 100 nm in FaSSIF media. In a side-by-side diffusion test, these nanoparticles produced a four-fold increase in niclosamide diffusion. We successfully manufactured amorphous extrudates of the poor glass former niclosamide that showed remarkable in vitro dissolution and diffusion performance. These in vitro tests were translated to a rat model that also showed an increase in oral bioavailability.

Unlike Hymenolepis nana that transmits directly from person to person, the transmission of Hymenolepis diminuta to human is via accidentally ingesting of arthropods carrying cysticercoid larvae as intermediate host. In places with poor hygienic conditions, this cestod may cause seldom infections especially in children. Studies carried out on various populations have reported the prevalence rate of H.diminuta between 0.001% and 5.5%. Although the reported cases are mostly children, the disease can be seen in every age group. In this report, a pediatric case of H.diminuta infection is presented. A twenty one-month-old male patient with the symptoms of vomiting 3-4 times a day along with mud-like diarrhea continuing for a week was admitted to the pediatric outpatient clinic. According to the history, it was learned that the house where he lived was above a barn and there was a history of insect swallowing. Laboratory findings revealed iron-deficiency anemia. The macroscopic appearance of the stool was in a pale clay-like form, and by direct microscopic examination with lugol solution, 70-75 μm in diameter, thick-shelled and six central hookleted eggs that are characteristic for H.diminuta were identified. A six-day course of oral niclosamide was administered to the patient beginning with 500 mg on the first day and 250 mg on the following five days, together with the treatment for the iron deficiency anemia. After fifteen days, the oral niclosamide treatment was repeated. No H.diminuta eggs were detected in the parasitological examination performed one month after completion of the second round of treatment. This case has been presented to call attention to the importance of patient anamnesis and microscopic examination in the diagnosis of H.diminuta infection which is a rarely seen parasitosis.

Hymenolepis diminuta also known as rat tapeworm rarely causes hymenolepiasis in humans. We report a case of H. diminuta infection in an 18-year-old male farmer who presented with intermittent pruritic maculopaular rashes and dull aching left iliac fossa pain for 6 months. Patient was cured with 2 doses of praziquantel 20 mg/kg on day 0 and 7.

Parasitic infestations of the galdbladder and biliary tract are quite rare. Taenia saginata is an intestinal helmint and patients harbouring adult T.saginata tapeworms are mostly asymptomatic and discharge only fecal proglottids. In some cases there might be nonspecific symptoms like vomiting, nausea, epigastric pain, diarrhea and weight loss. Tenia saginata is a also rare cause of ileus, pancreatitis, cholecystitis and cholangitis. We report a case of acute cholangitis caused by T. saginata presenting with fever, nausea, vomiting, jaundice and right upper quadrant pain. Although parasites are not an uncommon cause of cholangitis especially in diseaseendemic areas like the Far East, this is not true for T. saginata causing acute cholangitis.

We report a case of Hymenolepis diminuta infection in a 2-year-old child living in a suburban area of Catania, Italy. This case was initially referred to us as Dipylidium caninum infection, which was not cured after being treated twice with mebendazole. However, by analyzing the clinical presentation and stool samples we arrived to the diagnosis of H. diminuta infection. The case presented with atypical allergic manifestations which had never been reported as clinical features of symptomatic H. diminuta infection; remittent fever with abdominal pain, diffuse cutaneous itching, transient thoracic rash, and arthromyalgias. The patient was treated with a 7-day cycle of oral niclosamide, which proved to be safe and effective. This case report emphasizes that a correct parasitological diagnosis requires adequate district laboratories and trained personnel. In addition, we recommend the importance of reporting all H. diminuta infection cases, in order to improve knowledge on epidemiology, clinical presentation, and treatment protocols.

The most frequent symptom of taeniasis is the discharge of proglottids (93.7%). Gravid proglottids which do not have uterine pores are damaged when they exit the anus by their movement. Because of this damage most of the eggs contaminate the perianal tract. The cellophane tape technique that is used for getting perineum material is also a convenient technique for diagnosis of taeniasis. A 36 year-old woman was admitted to our parasitology clinic complaining of a watering mouth for one year, of abdominal pain, and of loss of appetite for 6 months, and who had discharged proglottids from time to time. She had been eating raw meat since her childhood and had had treatment for taeniasis fifteen years ago. She has also been under treatment for obsessive and compulsive neurosis and depression for two years and complained of constipation that was the side effect of the drug clomipramine HCL. She was given treatment with niclosamide and purgative treatment. The result of the treatment was incomplete because the patient refused to use the purgative. She was called for follow up controls two weeks and six months after treatment and after six months did not have any evidence of infection in her stools. When she was asked, the patient said that she did not need to use the drugs for the treatment of obsessive and compulsive neurosis and depression any more since her symptoms had decreased. According to various authorities, taeniasis is thought to be the cause of psychiatric symptoms due to its neural and psychological effects. These claims have been confirmed in our case because of her psychiatric symptoms decreased after the taeniasis treatment. Thus, the view that there is a relationship between intestinal parasites and psychiatric disease has been strengthened.

A 61-year-old eutrophic male was diagnosed with vitamin B12 deficiency and megaloblastic anemia. A modified Schilling test suggested intestinal malabsorption unrelated to intrinsic factor deficiency. Subsequent colonoscopy revealed the presence of a Taenia tapeworm. The anemia resolved within days under therapy with niclosamide and temporary vitamin B12 supplements. The present case suggests that, in addition to other well-known parasitic agents, e.g., Diphyllobothrium latum and Giardia lamblia, Taenia infestation can also be a cause of intestinal vitamin B12 malabsorption.

A thirteen-year old girl presented with acute right lower quadrant abdominal pain for which evaluation suggested appendicitis. At laparotomy, the appendix was normal but a Meckel\'s diverticulum with an impacted Taenia saginata (tapeworm) was found. The diverticulum was excised and histopathology confirmed diverticulitis from the parasite. Though Meckel\'s diverticulitis due to parasites has been reported, this is usually from ascaris. Tapeworm causing this complication is rare.