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

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

Pharmacologic and clinical evaluation of posaconazole.

Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. There is evidence of efficacy in the treatment and prevention of rarer, more difficult-to-treat fungal infections. Posaconazole oral suspension solution has shown limitations with respect to fasting state absorption, elevated gastrointestinal pH and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide an attractive treatment option by reducing interpatient variability and providing flexibility in critically ill patients. On the basis of clinical experience and further clinical studies, posaconazole was found to be a valuable pharmaceutical agent for the treatment of life-threatening fungal infections. This review will examine the development history of posaconazole and highlight the most recent advances

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

Drug interactions between direct-acting oral anticoagulants and calcineurin inhibitors during solid organ transplantation: considerations for therapy

Introduction: There is a high incidence of venous thromboembolism (VTE) in solid organ transplant recipients. The safety and efficacy of direct-acting oral anticoagulants (DOAC) have been well established in clinical practice for the prevention and treatment of VTE in broad populations. However, the management of VTE in the setting of solid organ transplantation remains a challenge to clinicians due to limited evidence of DOAC usage with calcineurin inhibitors. Areas covered: The current literature available on the pharmacokinetic-pharmacodynamic interaction between DOACs and calcineurin inhibitors is presented. A comprehensive review was undertaken using PubMed, Embase, drug product labeling, and drug product review conducted by the US Food and Drug Administration using Drugs@FDA. The potential for mitigation strategies and clinical management using extant knowledge is explored. Expert Opinion: Immunosuppression therapy is necessary to prevent graft rejection by the host. The sparsity of data together with the lack of well-designed prospective studies of DOAC use in solid organ transplant recipients presents a unique challenge to clinicians in determining the clinical relevance of possible drug interactions. Existing evidence suggests that with attention to concomitant drug use and renal function, the co-administration of DOACs and calcineurin inhibitors is safe and effective

Prediction of Sublingual Bioavailability of Buprenorphine in Newborns with Neonatal Abstinence Syndrome—a case study on physiological and developmental changes using NONMEM and SIMCYP

Poster presented at 2009 American College of Clinical Pharmacology conference in Orlando. April 24-28. Background: About 55 to 94% of infants born to opioid dependent mothershave neonatal abstinence syndrome (NAS). Buprenorphine (BUP) is usedclinically as an analgesic and a detoxification agent and a maintenancetreatment for opioid dependence. No data, however, has been reported about the use of sublingual administration of BUP below the age of 4 year, especially for term infants with NAS. Objectives: Characterize pharmacokinetics (PK) of BUP in newborn patients;Evaluate the developmental changes in newborns in order to assist dosingoptimization in ongoing clinical studies. Methods: In silico prediction of PK behavior and physiological development in newborn patients were evaluated using SIMCYP. Intravenous clearance was predicted through physiologically based simulation method in SIMCYP. Basedon sublingual clearance obtained from a one compartmental model developedpreviously using NONMEM, individual changes of sublingual bioavailability were evaluated with physiological development in the first one and half month during the newborn period. Results: Intrinsic clearance of BUP in newborns were incorporated into enzymekinetic data obtained from literature. Change of sublingual bioavailability fornewborns was evaluated with bioavailability-postmenstrual age profiles.Sublingual bioavailability of BUP was estimated as 8.9--56.6% in newborn patients studied during the first one and half postnatal month. Conclusion: Developmental considerations for the PK of BUP in newborns are important for the characterization of the dose-exposure relationship. We have evaluated this from “bottom-up” and “top-down” approaches with SIMCYP and NONMEM respectively and found these approaches to be complementary andvaluable for clinical trial design and routine clinical care. Presumably theywould facilitate rational decision making in pediatric drug development as well