An Approach for Improving the Detection and Quantitation of Buprenorphine and Its Metabolites in Maternal and Neonatal Hair.

Background: Buprenorphine (BUP) use is prevalent in pregnant women with opioid use disorder (OUD). Drug monitoring during pregnancy is critical for optimizing dosing regimen and achieving the desired clinical outcomes. Hair can be used as a critical biological matrix for monitoring long-term exposure to drugs.

Vaginal administration of 17-alpha hydroxyprogesterone caproate appears to be safe in non-pregnant female rats and rabbits.

Intramuscular (250 mg once weekly) or subcutaneous (275 mg once weekly) injections of 17-hydroxyprogesterone caproate (17-OHPC) has been utilised to prevent recurent spontaneous preterm birth in pregnant women with a short cervix or those with a prior preterm birth but its efficacy in these conditions has been questioned. It is unclear whether adequate concentrations of 17-OHPC reach the suspected target organs such as the cervix and uterus following either IM or SC administration.The objective of this study was to determine feasibility and safety of vaginal administration of 17-OHPC in adult female Sprague Dawley rats and female New Zealand rabbits.

Optimizing drug therapy during pregnancy: a spotlight on population pharmacokinetic modeling.

Introduction: Optimizing drug therapy during pregnancy is crucial for ensuring the safety of mothers and babiesPhysiological changes that occur during pregnancy can significantly alter the pharmacokinetics of medications. Population pharmacokinetic (PopPK) modeling is a valuable tool to guide drug dosing regimens in pregnant women.

Areas Covered: This narrative review summarizes the current literature on the application of PopPK modeling to optimize drug therapy during human pregnancy.

Evaluation of Effective Half-Life and Its Impact on Time to Steady State for Oral MeltDose Tacrolimus (LCPT) in De Novo Kidney Transplant Recipients.

Background: For extended-release drug formulations, effective half-life (t 1/2eff ) is a relevant pharmacokinetic parameter to inform dosing strategies and time to reach steady state. Tacrolimus, an immunosuppressant commonly used for the prophylaxis of organ rejection in transplant patients, is available as both immediate- and extended-release formulations. To the best of our knowledge, the t 1/2eff of tacrolimus from these different formulations has not yet been assessed.

Everolimus Personalized Therapy: Second Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.

The Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology established the second consensus report to guide therapeutic drug monitoring (TDM) of everolimus (EVR) and its optimal use in clinical practice 7 years after the first version was published in 2016. This version provides information focused on new developments that have arisen in the last 7 years. For the general aspects of the pharmacology and TDM of EVR that have retained their relevance, readers can refer to the 2016 document.

A Pharmacologic Evaluation of Buprenorphine in Pregnancy and the Postpartum Period.

Background: The dosing regimen in the package insert for sublingual buprenorphine is similar for pregnant and nonpregnant people despite the physiologic changes seen during pregnancy.

Aims: To compare plasma buprenorphine pharmacokinetics during and after pregnancy and relate buprenorphine concentration to the pharmacodynamic endpoints of pupil diameter, Clinical Opioid Withdrawal Scale (COWS), and craving scores.

Study Design: Prospective cohort of 22 pregnant people undergoing 33 pharmacologic studies (6-8 hours each) during pregnancy or postpartum.

Drugs in Human Milk Part 1: Practical and Analytical Considerations in Measuring Drugs and Metabolites in Human Milk.

Human milk is a remarkable biofluid that provides essential nutrients and immune protection to newborns. Breastfeeding women consuming medications could pass the drug through their milk to neonates. Drugs can be transferred to human milk by passive diffusion or active transport.

The dosing regimen for 17-hydroxyprogesterone caproate was suboptimal: lessons for future pharmacotherapy for pregnant women.

Background: Makena (17-hydroxyprogesterone caproate) was approved by the United States Food and Drug Administration for the prevention of recurrent spontaneous preterm birth in 2011 under the accelerated approval pathway, but fundamental pharmacokinetic or pharmacodynamic (Phase 1 and Phase 2) studies were not performed. At the time, there were no dose-response or concentration-response data. The therapeutic concentration was not known.

Selection of a suitable animal model to evaluate secretion of drugs in the human milk: a systematic approach.

Lack of data on drug secretion in human milk is a concern for safe use of drugs during postpartum.Clinical studies are often difficult to perform; despite substantial improvements in computational methodologies such as physiologically based pharmacokinetic modelling, there is limited clinical data to validate such models for many drugs.Various factors that are likely to impact milk to plasma ratio were identified.

Simplified processing and rapid quantification of buprenorphine, norbuprenorphine, and their conjugated metabolites in human plasma using UPLC-MS/MS: Assessment of buprenorphine exposure during opioid use disorder treatment.

Opioid use disorder (OUD) is a chronic neurobehavioral ailment and is prevalent in pregnancy. OUD is commonly treated with methadone or buprenorphine (BUP). Pregnancy is known to alter the pharmacokinetics of drugs and may lead to changes in drug exposure and response.

Topical Tacrolimus and Mycophenolic Acid Therapy Synergizes with Low Dose Systemic Immunosuppression to Sustain Vascularized Composite Allograft Survival.

Aim: The goal of this study was to evaluate whether topical administration of tacrolimus (TAC) and mycophenolic acid (MPA) at the transplant site enables vascularized composite allograft (VCA) survival with significant minimization of the dose and adverse effects of systemic TAC (STAC) immunosuppression.

Materials And Methods: Lewis (Lew) rats received orthotopic hind limb allotransplants from fully mismatched Brown Norway (BN) donors. Group 1 (Controls) received no treatment.

Nerve Wrap for Local Delivery of FK506/Tacrolimus Accelerates Nerve Regeneration.

Peripheral nerve injuries (PNIs) occur frequently and can lead to devastating and permanent sensory and motor function disabilities. Systemic tacrolimus (FK506) administration has been shown to hasten recovery and improve functional outcomes after PNI repair. Unfortunately, high systemic levels of FK506 can result in adverse side effects.

A systematic review of pregnancy-related clinical intervention of drug regimens due to pharmacokinetic reasons.

Background And Objective: Published works have discussed the pharmacokinetic interactions of drugs with pregnancy, but none comprehensively identify all the approved United States Food and Drug Administration (FDA) and European Medicines Administration (EMA) drugs that have a pregnancy-related intervention. The objective of this systematic review is to comprehensively identify medications that have clinically meaningful interventions due to pharmacokinetic reasons.

Methods: An in-depth search of clinical data using the PDR3D: Reed Tech Navigator™ for Drug Labels was conducted from 1 June to 12 August 2022.

Challenges in Conducting Therapeutic Trials in Pregnancy: Emphasizing Recent Lessons Learned.

Pregnant people have traditionally been excluded from therapeutic research by restrictions intended for fetal protection. Despite a movement toward inclusion, concerns for the feasibility and safety of including pregnant people in studies continue to limit this research. This article reviews the history of research guidelines in pregnancy and illustrates ongoing challenges, as seen in the development of vaccines and therapies during the coronavirus disease 2019 pandemic and investigation of statins for preeclampsia prevention.

Simultaneous quantitation of ketamine, norketamine and dehydronorketamine in human milk using a novel ultra high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay.

There is a paucity of data on the transfer of ketamine from maternal blood into human milk. Quantification of ketamine in human milk provides information about the potential exposure of the infant to ketamine and its metabolites from the mother during lactation. A highly specific, reproducible, and sensitive UPLC-MS/MS based analytical method was developed and validated for the quantitation of ketamine and its metabolites (norketamine and dehydronorketamine) in human milk.

Relationship between plasma concentration of 17-hydroxyprogesterone caproate and gestational age at preterm delivery.

Background: The effectiveness of 17-hydroxyprogesterone caproate is unclear as trials have provided conflicting results. With the absence of fundamental pharmacologic studies addressing dosing or the relationship between drug concentration and gestational age at delivery, the effectiveness of the medication cannot be evaluated.

Objective: This study aimed to evaluate the relationship between plasma concentrations of 17-hydroxyprogesterone caproate and preterm birth rates and gestational age at preterm delivery and to assess the safety of the 500-mg dose.

Intra-amniotic sildenafil administration in rabbits: Safety, pharmacokinetics, organ distribution and histologic evaluation.

Background: The effectiveness of sildenafil in the management of pulmonary hypertension in congenital diaphragmatic hernia (CDH) has been reported but has not been systematically evaluated. Our studies have also demonstrated that intra-amniotic (IA) sildenafil administration improves pulmonary hypertension in CDH.

Methods: We evaluated the pharmacokinetics of sildenafil after IA administration in pregnant rabbits.

A cocktail probe approach to evaluate the effect of hormones on the expression and activity of CYP enzymes in human hepatocytes with conditions simulating late stage of pregnancy.

Purpose: Pregnancy-mediated physiological and biochemical changes contribute to alterations in the pharmacokinetics of certain drugs. There is a paucity of data on the systematic evaluation of the underlying mechanisms. The objective of the current study was to examine the impact of changes in circulating and tissue hormonal concentration during the late stage of pregnancy on the activity and expression of hepatic cytochrome P450 (CYP) enzymes using a cocktail probe approach.

Effect of formulation and route of administration on the distribution of 17-hydroxyprogesterone caproate in rats.

Weekly intramuscular (250 mg/week) or subcutaneous (275 mg/week) injections of 17-hydroxyprogesterone caproate (17-OHPC) is the only treatment option for the prevention of preterm birth in women with a prior history of preterm delivery.The objective of the current study was to determine the relative distribution of 17-OHPC in selected tissues in adult female SD rats after IM (oily formulation or solution), IV (solution), PO (solution), or intravaginal (suppository) administration.Plasma, uterus, adipose, and liver samples were collected at various times and analysed by LC-MS-MS.

Applications of Volumetric Absorptive Microsampling Technique: A Systematic Critical Review.

Methods: A novel microsampling device called Volumetric Absorptive microsampling (VAMS), developed in 2014, appears to have resolved the sample inhomogeneity inherent to dried blood spots, with improved precision in the volume of sample collected for measuring drug concentration. A literature search was conducted to identify several analytical and pharmacokinetic studies that have used VAMS in recent years.

Results: The key factors for proper experimental design and optimization of the extraction of drugs and metabolites of interest from the device were summarized.

Renin-angiotensin-aldosterone system function in the pig-to-baboon kidney xenotransplantation model.

After pig-to-baboon kidney transplantation, episodes of hypovolemia and hypotension from an unexplained mechanism have been reported. This study evaluated the renin-angiotensin-aldosterone system post-kidney xenotransplantation. Kidneys from genetically-engineered pigs were transplanted into 5 immunosuppressed baboons after the excision of the native kidneys.

Effects of Pro-Inflammatory Cytokines on Hepatic Metabolism in Primary Human Hepatocytes.

Three decades of hepatocyte transplantation have confirmed such a cell-based approach as an adjunct or alternative treatment to solid organ transplantation. Donor cell survival and engraftment were indirectly measured by hepatospecific secretive or released metabolites, such as ammonia metabolism in urea cycle defects. In cases of sepsis or viral infection, ammonia levels can significantly and abruptly increase in these recipients, erroneously implying rejection.

Trajectories of Depressive and Anxiety Symptoms Across Pregnancy and Postpartum in Selective Serotonin Reuptake Inhibitor-Treated Women.

Objective: Tracking perinatal mood and anxiety disorders is championed by the American Psychiatric Association and the International Marcé Society for Perinatal Mental Health. We conducted this study to examine trajectories of monthly depressive and anxiety symptoms through pregnancy and postpartum.

Methods: This is a prospective longitudinal observational cohort study of pregnant women interviewed at baseline (≤18th gestational week), every four weeks through delivery and at 6 and 14 weeks postpartum at three urban academic medical centers ( = 85) and a single rural health center ( = 3) from 2016 to 2020.

The combination of exposure to Tacrolimus, mycophenolic acid, Inosine 5'-Monophosphate Dehydrogenase activity and inhibition in the first week define early histological outcomes in renal transplant recipients.

Therapeutic drug monitoring is routine for Tacrolimus, while levels are not routinely monitored for mycophenolic acid (MPA). This study investigated the effect of early post-transplant pharmacokinetics (PK) of MPA and Tacrolimus along with the pharmacodynamics (PD) of MPA on biopsy-proven acute rejection (BPAR) after renal transplantation. A prospective PK/PD study with limited sampling (three blood samples) was conducted in renal transplant recipients on week 1, around Day 6 (n = 42) and at the 3rd-month biopsy on Day 90 (n = 23).