The metabolism of the drug is as such: once the drug enters the target infected cell, Brincidofovirs phosphodiester bond is then hydrolyzed to generate cidofovir which is then phosphorylated to the active cidofovir diphosphate. The volume of distribution of the drug is 1230 L. Brincidofovir is almost entirely absorbed in plasma. History
Because smallpox is eradicated, the effectiveness of brincidofovir was studied in animals infected with viruses that are closely related to the variola virus. Effectiveness was determined by measuring animals survival at the end of the studies.Safety information to support approval of brincidofovir was derived from clinical trials of the drug for a non-smallpox indication, primarily from patients who received hematopoietic stem cell transplants.The U.S. Food and Drug Administration (FDA) granted the application for brincidofovir priority review, fast track, and orphan drug designations. The FDA approved brincidofovir under the agencys Animal Rule, which allows findings from adequate and well-controlled animal efficacy studies to serve as the basis of an approval when it is not feasible or ethical to conduct efficacy trials in humans. Ethical considerations
Brincidofovir (CMX001) was the subject of widespread social media campaigning in 2014, which was then picked up by national news sources about a boy with an adenovirus infection following a bone marrow transplant. The family requested legal access to the still-unapproved drug outside of any clinical trial, and Chimerix initially denied the request. After a short and intense media campaign, Chimerix got permission from the FDA to start a limited open-label trial which allowed the boy to receive the drug.
Although most causes are relatively benign, Horners syndrome may reflect serious disease in the neck or chest (such as a Pancoast tumor (tumor in the apex of the lung) or thyrocervical venous dilatation).Causes can be divided according to the presence and location of anhidrosis:
Central (anhidrosis of face, arm and trunk)
Syringomyelia
Multiple sclerosis
Encephalitis
Brain tumors
Lateral medullary syndrome
Preganglionic (anhidrosis of face)
Cervical rib traction on stellate ganglion
Thyroid carcinoma
Thyroidectomy
Goiter
Bronchogenic carcinoma of the superior fissure (Pancoast tumor) on apex of lung
Klumpke paralysis
Trauma - base of neck, usually blunt trauma, sometimes surgery. As a complication of tube thoracostomy
Thoracic aortic aneurysm
Postganglionic (no anhidrosis)
Cluster headache - combination termed Hortons headache
An episode of Horners syndrome may occur during a migraine attack and be relieved afterwards
Carotid artery dissection/carotid artery aneurysm/trauma
Cavernous sinus thrombosis
Middle ear infection
Sympathectomy
Nerve blocks, such as cervical plexus block, stellate ganglion or interscalene block

Pathophysiology
Horner syndrome is due to a deficiency of sympathetic activity. The site of lesion to the sympathetic outflow is on the ipsilateral side of the symptoms. The following are examples of conditions that cause the clinical appearance of Horners syndrome:
First-order neuron disorder: Central lesions that involve the hypothalamospinal tract (e.g. transection of the cervical spinal cord). Second-order neuron disorder: Preganglionic lesions (e.g. compression of the sympathetic chain by a lung tumor) that releases acetylcholine. Third-order neuron disorder: Postganglionic lesions at the level of the internal carotid artery (e.g. a tumor in the cavernous sinus or a carotid artery dissection) that releases norepinephrine.