Safety, Tolerability, and Pharmacokinetic Study of 101BHG-D01 Nasal Spray, a Novel Long-Acting and Selective Cholinergic M Receptor Antagonist, in Healthy Chinese Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Single-Dose Escalation, First-In-Human Study.

BACKGROUND AND OBJECTIVE: 101BHG-D01 nasal spray is the first novel long-acting cholinergic M receptor antagonist under development to treat rhinorrhea in rhinitis. This first-in-human study aimed to evaluate the safety, tolerability, and pharmacokinetics of 101BHG-D01 nasal spray following single intranasal doses in healthy Chinese subjects. METHODS: A randomized, double-blind, placebo-controlled, single-dose escalation study was conducted in healthy Chinese volunteers after intranasal doses of 101BHG-D01 nasal spray or placebo ranging from 40 µg to 960 µg (total of six doses). Blood samples were collected at scheduled time points, and plasma concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. A non-compartmental method was used to calculate the main pharmacokinetic parameters, including the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t), the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), the maximum plasma concentration (Cmax), the time to maximum plasma concentration (Tmax), and the elimination half-life (t1/2). Safety was evaluated by monitoring adverse events, laboratory assays, vital signs, physical examinations, 12-lead electrocardiograms (ECGs), anterior rhinoscopy, ophthalmic examination, and ambulatory ECG monitoring. RESULTS: Following single intranasal dosing, 101BHG-D01 was rapidly absorbed with a median Tmax of 0.34-0.50 h and eliminated slowly with a mean t1/2 ranging from 4.29 to 46.76 h for different dose groups. The Cmax and AUC of 101BHG-D01 increased linearly across the examined dose range of 40-960 µg. 101BHG-D01 nasal spray was well tolerated, all AEs were mild, and no serious adverse events occurred during the study. CONCLUSIONS: 101BHG-D01 nasal spray was safe and well tolerated in healthy Chinese subjects when administered intranasally in single escalating doses. The mean Cmax and AUC increased proportionally to the studied dose. The pharmacokinetic, safety, and tolerability profiles of 101BHG-D01 nasal spray indicate that it is a good candidate for further development as a treatment for rhinorrhea in rhinitis.

[Endovascular repair of an iliac artery aneurysm after endovascular aneurysm repair with handmade iliac branch device: a case report].

An involved internal iliac artery is usually embolized when performing endovascular aneurysm repair for aortoiliac or isolated iliac artery aneurysm.This can lead to complications such as buttock claudication,colon ischaemia and erectile dysfunction.Iliac branch device (IBD) is an endograft designed specifically for iliac bifurcation to preserve internal iliac flow. It was performed with high technical success rates and encouraging mid-term patency. Here we report a case of right iliac aneurysm developed 3 years after endovascular aneurysm repair for an aortoiliac aneurysm, with the patient's left internal artery been sacrificed then. Using a handmade IBD, we excluded the aneurysm without occlusion of the ipsilateral internal iliac artery or any type of endoleak. Both the design and deployment of this IBD are distinctive that we would like to share our experience with all the colleagues.

[Endovascular treatment of a rare type of aortic arch aneurysm derived from the fourth aortic arch].

OBJECTIVE: To report a rare type of aortic arch aneurysm. METHODS: Three cases of aortic arch aneurysm derived from the fourth aortic arch were retrospectively analyzed. The pathogenesis and treatment of this type of aortic arch aneurysm were investigated. RESULTS: Most of the aneurysm body was located in the Z2 zone, which was the stem from the fourth aortic arch in the embryonic development period. All of the 3 cases could not be explained by common etiology. We speculated that the cause might be developmental anomaly of the fourth aortic arch. All the 3 aortic arch aneurysms were totally excluded with a covered stent. The technical success rate was 100%. Endoleak of type I was seen in one case, which was resolved in a later open surgery. During the follow-up, no type of complications was found. CONCLUSION: To the best of our knowledge, this is the first report of this type of aortic arch aneurysm. The cause may be developmental anomaly of the fourth aortic arch. Endovascular treatment of this type of aortic arch aneurysm is feasible.

[CT and MRI diagnosis of congenital stenosis of the internal auditory canal].

OBJECTIVE: To investigate multiple slice computed tomography (MSCT) and magnetic resonance imaging (MRI) features of congenital stenosis of the internal auditory canal (CSIAC) and improve the ability for diagnosis. METHOD: Thirteen cases with fifteen ears were studied. In all cases a MSCT and MRI was performed. RESULTS: Eleven cases were unilateral, and 2 cases were bilateral. MSCT could show the narrowness of IAC. Three cases were isolated, but the others were combined with inner ear malformations. One ear had inner, middle and outer ear malformations. One ear had inner, middle, and outer ear malformations with a frontal bone malformation. MRI demonstrated that all of the vestibulocochlear nerves were hypoplastic. The cochlear nerve in seven ears was not present, in seven ears the nerve was thinner, and in the last case it was poorly visualized. The facial nerve in two ears was hypoplastic. Volume rendering (VR) could present the degree of the narrowed internal auditory canals, combined with other inner ear anomalies. CONCLUSION: MSCT will show the degree of the narrow internal auditory canals and combined anomalies, while the MRI can further demonstrate the nerves' development.

[Imaging features of duplication of the internal auditory canal].

OBJECTIVE: To explore multiple slices computed tomography (MSCT) and magnetic resonance imaging (MRI) features of duplication of the internal auditory canal (DIAC) in order to improve the accuracy of diagnosis. METHODS: Four cases (5 ears) were analyzed and the related documents were reviewed retrospectively. MSCT was performed on all cases, and two cases had MRI scanning at the same time. RESULTS: MSCT has shown that the internal auditory canal were divided into two canals by a bony septum in 5 ears. The superior canal ended in a very narrow connection to the facial canal, the inferior portion ended in connection to the cochlea and vestibule. The bony septums from the 2 ears were found no longer intact. The sum of diameter of the two canals was greater than 2 mm. In addition, 5 ears were found to have an enlarged vestibules and the hypoplasia lateral semicircular canals, and meanwhile, 2 ears of them were combined with ipsilateral microtia. Also 1 case of them was combined with microtia, outer acoustic atresia as well as abnormal middle ear. Multiplanar reconstruction and volume rendering images can entirely show the bony septum and two canals. In this study, the vestibular nerve, cochlear nerve and facial nerve were total hypoplastic in one ear, in the other ear, the vestibular and cochlear nerve were hypoplastic, and however, the facial nerve was intact. CONCLUSIONS: MSCT can clearly depict duplication of the internal auditory canals and concomitant anomalies. MRI can clearly show the neural components and their associated malformation.