Buprenorphine in Neonatal Abstinence Syndrome.

Infants exposed in utero to opioids will demonstrate a withdrawal syndrome known as neonatal abstinence syndrome (NAS). Buprenorphine is a long-acting opioid with therapeutic use in medication-assisted treatment of opioid dependency in adults and adolescents. Emerging data from clinical trials and treatment cohorts demonstrate the efficacy and safety of sublingual buprenorphine for those infants with NAS who require pharmacologic treatment. Pharmacometric modeling will assist in defining the exposure-response relationships and facilitate dose optimization

Tumor necrosis factor inhibitors in psoriatic arthritis.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory disease that can result in significant disability. With the emergence of tumor necrosis factor inhibitors (TNFi), therapeutic outcomes in PsA have improved substantially. The clinical efficacy and the inhibition of radiographic progression demonstrated by TNFi have transformed the management of PsA. However, there is still an unmet need for a subset of patients who do not respond adequately to TNFi. Areas covered: This review provides an overview of the pharmacokinetics of TNFi, the efficacy of TNFi in PsA, and the role of immunogenicity of TNFi in the treatment of PsA. In addition, we address the use of TNFi in the setting of other medications utilized in the treatment of PsA and the potential future role of biosimilars. Expert commentary: Monoclonal antibodies exhibit complex and widely variable pharmacokinetics. The study of factors that can affect the pharmacokinetics, such as immunogenicity, is valuable to further define and understand the use of TNFi in PsA, especially in the subset of patients who do not respond adequately to these agents or lose effectiveness over time

An analysis of the passenger vehicle interface of street transit systems with applications to design optimization

This research analyzes the Passenger Vehicle Interface of the street transit systems and presents applications for design optimization. The Passenger Vehicle Interface (PVI) is defined as the interaction between the passenger and vehicle elements of the street transit system. Human observer and photographic studies were conducted in 17 cities in the United States and Canada to measure the time for queues of passengers to board various transit vehicles. The data were analyzed by considering seven factors that affect the Passenger Vehicle Interface: Human Factor, Modal Factor, Operating Practices, Operating Policies, Mobility, Climate and Weather, and Other System Elements. Those effects which could be quantified were divided into the categories of direction of flow, method of fare collection, and door characteristics and use. A series of equations for each of these categories was developed to predict passenger service time when the number of alighting or boarding passengers is known or estimated. A range of values was developed for the parameters of each equation to reflect the effects of unquantifiable factors such as the type of passenger, physical characteristics of the passenger, passenger preferences, baggage carried, seating configuration, and congestion. The use of Passenger Influence Zones has indicated that passenger service time can range from approximately six to 14 percent of total trip time, depending upon vehicle type, door use, and method of fare collection. These zones have also been used to indicate how vehicle door use and characteristics can increase berth requirements by up. to 200 percent, and New different methods of fare collection can increase berth productivity in terms of passengers per hour by 87 percent. Distributions of passenger service times through the vehicle doors were identified based on the analysis of photographic studies and determined to be represented by an Erlang function. The analysis also inferred that the K value in the Erlang function is equal to the number of doors on the vehicle and that the minimum service time is approximately equal to half the average service time. The validity of the Erlang functions was determined by using the special purpose simulation programming language, GPSS, and the Erlang functions to estimate the time requirements for queues of passengers to board vehicles. The simulated times were compared with observed times, and the differences were found to be not statistically significant at the 95 percent level. A GPSS model was used to simulate the operations of a street tran sit loading area and to evaluate the effects of method of fare collection upon queue length and average waiting time under varying rates of passenger arrivals. This research provides sufficient information to perform sub- optimizations of several operations within the Passenger Vehicle Interface. Although not directed toward an optimization of street transit systems, it does provide the necessary information about the Passenger Vehicle Interface for others to perform this optimization after they have assembled comparable information on system elements and other interactions

Neonatal abstinence syndrome: Pharmacologic strategies for the mother and infant.

Opioid use in pregnancy has increased dramatically over the past decade. Since prenatal opioid use is associated with numerous obstetrical and neonatal complications, this now has become a major public health problem. In particular, in utero opioid exposure can result in neonatal abstinence syndrome (NAS) which is a serious condition characterized by central nervous system hyperirritability and autonomic nervous system dysfunction. The present review seeks to define current practices regarding the approach to the pregnant mother and neonate with prenatal opiate exposure. Although the cornerstone of prenatal management of opioid dependence is opioid maintenance therapy, the ideal agent has yet to be definitively established. Pharmacologic management of NAS is also highly variable and may include an opioid, barbiturate, and/or α-agonist. Genetic factors appear to be associated with the incidence and severity of NAS. Establishing pharmacogenetic risk factors for the development of NAS has the potential for creating opportunities for personalized genomic medicine and novel, individualized therapeutic interventions

Ethanol Pharmacokinetics in Neonates and Infants

Introduction: Ethanol has been used for years in neonatal and infant liquid medications, yet the pharmacokinetics, pharmacodynamics, and safety of ethanol in this vulnerable population have not been well characterized. The purpose of this review is to raise awareness of ethanol use as an excipient in neonatal and infant medications and to provide insight, based on the available evidence, into clearance rates of ethanol in babies. We also discuss ethanol pharmacokinetics in adults, theoretical pharmaco-kinetic changes in neonates and infants as it may apply to ethanol disposition, and case reports involving ethanol exposure in neonates and infants. Materials and methods: This study was a narrative review in which relevant papers were selected using databases and scientific search engines such as PubMed with the key words ethanol, infant, and newborn infant. Results: It remains unclear what ethanol exposure is safe for neonates and infants. The Food and Drug Administration and American Academy of Pediatrics have both taken action, by either setting limits of ethanol content in over-the-counter medications or by recommending restricted exposure to ethanol- containing pediatric formulations. Conclusions: Until the short- and long-term health effects of chronic ethanol administration can be further characterized, ethanol-containing medications should be used with caution

Pharmacologic management of the opioid neonatal abstinence syndrome.

Opioid use in pregnant women has increased over the last decade. Following birth, infants with in utero exposure demonstrate signs and symptoms of withdrawal known as the neonatal abstinence syndrome (NAS). Infants express a spectrum of disease, with most requiring the administration of pharmacologic therapy to ensure proper growth and development. Treatment often involves prolonged hospitalization. There is a general lack of high-quality clinical trial data to guide optimal therapy, and significant heterogeneity in treatment approaches. Emerging trends in the treatment of infants with NAS include the use of sublingual buprenorphine, transition to outpatient therapy, and pharmacogenetic risk stratification

The pharmacokinetics of nebulized nanocrystal budesonide suspension in healthy volunteers.

Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg were approximately dose proportional with respect to Cmax, AUC(0-t), and AUC(0-infinity). Nanobudesonide 0.5 mg and Pulmicort Respules 0.5 mg exhibited similar AUCs, suggesting a similar extent of pulmonary absorption. A higher Cmax was noted with nanobudesonide 0.5 mg, and the tmax was significantly different, suggesting a more rapid rate of drug delivery of nanobudesonide 0.5 mg than Pulmicort Respules. In conclusion, nebulized nanobudesonide 0.5 mg was safe in healthy volunteers, with a similar extent of absorption as Pulmicort Respules

Vancomycin in peritoneal dialysis: Clinical pharmacology considerations in therapy.

Intraperitoneal vancomycin is the first-line therapy in the management of peritoneal dialysis (PD)-related peritonitis. However, due to the paucity of data, vancomycin dosing for peritonitis in patients on automated peritoneal dialysis (APD) is empiric and based on clinical experience rather than evidence. Studies in continuous ambulatory peritoneal dialysis (CAPD) patients have been used to provide guidelines for dosing and are often extrapolated for APD use, but it is unclear whether this is appropriate. This review summarizes the available pharmacokinetic data used to inform optimal dosing in patients on CAPD or APD. The determinants of vancomycin disposition and pharmacodynamic effects are critically summarized, knowledge gaps explored, and a vancomycin dosing algorithm in PD patients is proposed