Objective.-This study evaluated the pharmacokinetic and tolerability profiles of Zelrix™ (NuPathe Inc., Conshohocken, PA, USA), the novel formulation of sumatriptan (formerly known as NP101).Background.-Migraine is an episodic headache disorder characterized by a combination of neurological, gastrointestinal, and autonomic symptoms. Gastrointestinal disturbances, including nausea, vomiting, and gastric stasis are common and can result in significant impact on treatment. Triptans are 5-hydroxytriptanime1B/1D agonists that work on the trigeminal nerve that is activated during migraine. All triptans approved for use in the US are currently available as oral formulations; however, this may not be the ideal route of administration for many migraineurs. Sumatriptan is also available as a nasal spray and subcutaneous (sc) injection. Therefore, the need to develop improved methods for noninvasive parenteral delivery of triptans remains high.Methods.-This was a Phase I, single-center, open-label, crossover study that assessed the pharmacokinetic properties of a single dose of sumatriptan delivered using an iontophoretic transdermal patch in comparison with oral, injection, and nasal delivery. Subjects were healthy male and female volunteers who received each of 5 treatments: sumatriptan 100 mg oral tablets, sumatriptan 6 mg sc, sumatriptan 20 mg nasal spray, Zelrix I (transdermal patch with 3 g of gel solution delivering 6 mg of sumatriptan transdermally), or Zelrix II (transdermal patch containing 2.6 g of gel solution delivering 6 mg of sumatriptan).Results.-The C max for Zelrix was reduced to 30% and 28% of the sumatriptan sc dose, thereby reducing the risk of triptan-like sensations associated with high peak plasma concentrations. Plasma concentrations for Zelrix I and Zelrix II were intermediate between those for oral and nasal sumatriptan doses tested. Transdermal patch delivery of sumatriptan to the systemic circulation reached plasma concentrations of 10 ng/mL within about 30 minutes. The mean drug delivery of Zelrix I and II was 6.11 mg (confidence intervals [CI] 5.33-6.88) and 6.09 mg (CI 5.52-6.66), respectively. The AUC0-inf was approximately 99% for the Zelrix I patch and 100% for the Zelrix II patch as compared with sumatriptan 6 mg sc dose. Both doses of sumatriptan transdermal patches were well tolerated. Skin reactions at the patch site were mild and erythema resolved in most subjects within 48-72 hours.Conclusions.-The results from this study show that sumatriptan administration using a novel iontophoretic transdermal technology delivers plasma levels within the range for nasal spray, tablet, and injectable sumatriptan. Zelrix I and II were well tolerated and adverse events were mild and transient. Transdermal delivery of sumatriptan using the SmartRelief iontophoretic technology may prove beneficial for a large segment of the migraine population based upon fast, consistent delivery of drug and avoidance of common gastrointestinal disturbances associated with migraine.
The adenoids removed from patients with RAOM had almost their entire mucosal surface covered with biofilms, versus scant coverage for patients with OSA. Recurrent acute otitis media is notoriously resistant to antibiotic treatment, and aspirates of middle ear fluid repeatedly yield negative cultures. It is these properties that have led biofilms to become increasingly implicated in the pathogenesis of RAOM. Thus, the resistance of biofilms to antimicrobials, together with their planktonic shedding of organisms, may be an important mechanism in the development of RAOM.
ObjectiveThe aim of this study was to investigate the role of obstructive sleep apnea (OSA) on all-cause mortality in patients with COPD.MethodsData for this cross-sectional study were obtained from the National Health and Nutrition Examination Survey (NHANES) data (year 2005–2008). Eligible subjects were ≥20 years who had no COPD or OSA (n=9,237), had only OSA (n=366), had only COPD (n=695), and had OSA/COPD overlap syndrome (n=90). Univariate and multivariate analyses were used to evaluate factors associated with overall mortality.ResultsMultivariate analysis found that the COPD and OSA/COPD overlap syndrome groups had significantly higher chance of all-cause mortality than the group of subjects who did not have OSA or COPD (adjusted hazard ratio [HR] =1.5 for the COPD group and 2.4 for the overlap syndrome group) (P≤0.007). Although not significant, having OSA/COPD overlap syndrome was associated with higher likelihood of death than COPD alone (HR =1.5; P=0.160). Other factors associated with higher overall mortality were aging, poorer family status, current smoker, serum vitamin D deficiency, cardiovascular disease, history of cancer, diabetes, and impaired renal function.ConclusionThe present study found that COPD and OSA/COPD overlap syndrome were associated with higher all-cause mortality compared with patients without either disease and that OSA did not significantly increase mortality in patients with COPD.
Budd-Chiari syndrome is an unusual form of portal hypertension caused by occlusion of the hepatic venous outflow, and it is often confused with portal hypertension caused by liver cirrhosis. Its prognosis is poor, and optimal therapy remains to be established. This is a report of 100 confirmed cases of this syndrome treated from December 1982 to March 1988 at two vascular centers in China. Sixty-two male and 38 female patients, 15 to 62 years of age (mean age, 32.6 years) were treated. Seventy-six patients had intractable ascites, 56 had esophageal varices, and 22 had upper gastrointestinal bleeding. There were 37 cases of membranous obstruction, 57 cases of occlusion of the inferior vena cava above the confluence of the hepatic veins, and 6 cases of occlusion of the hepatic veins. Eighty-one patients were operated on. Operative mortality rate was 8.6% (7/81). Follow-up from 2 to 66 months revealed that 58 of the patients operated on (72%) had good results, whereas 11 of 19 (58%) patients treated nonoperatively died within 2 months after admission. On the basis of these data we conclude that the operative procedure must be tailored to the cause and underlying pathologic characteristics. Mesoatrial shunting is the operation of choice for patients with occlusion of the retrohepatic inferior vena cava and hepatic veins, and inferior vena cava--atrial shunting is the operation of choice for patients with occlusion of the inferior vena cava and patency of the hepatic veins. Membranotomy is used for patients with inferior vena cava webbing, and mesocaval shunting is used for patients with intrahepatic venous occlusion only.(ABSTRACT TRUNCATED AT 250 WORDS)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.