Edmund Capparelli

• University of California, San Diego

Objectives To define meropenem plasma concentrations and pharmacodynamic exposure metrics in children with septic shock during the first 3 days of PICU hospitalization. Design Pharmacokinetic sampling was undertaken in 19 subjects receiving standard meropenem dosing (20 mg/kg/dose, 8 hr) recruited from March 2019 to March 2022. Sampling occurred o...

Background Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS. Methods VRC07523LS, 80 mg/dose, was administered subcutaneously after birth t...

Objectives To develop a pragmatic twice daily lamivudine dosing strategy for preterm infants from 24 to 37 completed weeks of gestation. Methods Data were combined from eight pharmacokinetic studies in neonates and infants receiving lamivudine oral solution. A population pharmacokinetic model was developed using non-linear mixed effects regression...

Introduction High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C0) and steady-state area-under-curve (AUC0-24) targets are important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used in clinical practice to p...

Pediatric dosing of enoxaparin was derived based on extrapolation of the adult therapeutic range to children. However, a large fraction of children do not achieve therapeutic anticoagulation with initial dosing. We aim to use real-world anti-Xa data obtained from children receiving enoxaparin per standard of care to characterize the population phar...

Objectives To confirm that levetiracetam (LEV) demonstrates predictable pharmacokinetics(PK) at higher doses and to study the pharmacodynamics(PD) of LEV. Design Pharmacokinetic data from the NEOLEV1 and NEOLEV2 trials were analysed using a non-linear mixed effects modelling approach. A post hoc analysis of the effect of LEV on seizure burden was...

After sporadic reports of post-treatment control of HIV in children who initiated combination anti-retroviral therapy (cART) early, we prospectively studied 284 very-early-cART-treated children from KwaZulu-Natal, South Africa, after vertical HIV transmission to assess control of viremia. Eighty-four percent of the children achieved aviremia on cAR...

Background Pregnant people with coronavirus disease 2019 (COVID-19) experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy. Methods IMPAACT 2032 was a phase 4 pr...

BACKGROUND Broadly neutralizing monoclonal antibodies (bNAbs) represent a promising strategy for HIV-1 immunoprophylaxis and treatment. 10E8VLS and VRC07-523LS are bNAbs that target the highly conserved membrane-proximal external region (MPER) and the CD4-binding site of the HIV-1 viral envelope glycoprotein, respectively.METHODS In this phase 1, o...

Background Study of liquid lopinavir/ritonavir (LPV/r) in young infants has been limited by concerns for its safety in neonates. Methods International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1106 was a phase IV, prospective, trial evaluating the safety and pharmacokinetics of antiretroviral medications administered according to...

Background: Clinical interpretation of the reduced dolutegravir (DTG) plasma concentrations reported during pregnancy is complicated by its high plasma protein binding. Plasma proteins significantly decrease during pregnancy, and understanding changes in DTG protein binding and its therapeutically active unbound concentrations are necessary to eva...

Background The primary objective of this study was to characterize meropenem (MERO) pharmacokinetics (PK) in critically ill infants and children with septic shock to develop dosing recommendations to achieve therapeutic drug exposure in this complex population with a spectrum of renal function from augmented renal clearance (ARC) to acute kidney in...

Physiological changes during pregnancy may alter the pharmacokinetics (PK) of antituberculosis drugs. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026s was a multicenter, phase IV, observational, prospective PK and safety study of antiretroviral and antituberculosis drugs administered as part of clinical care in pr...

Knowledge about exposure to cannabidiol (CBD) in breastfed infants can provide an improved understanding of potential risk. The aim was to predict CBD exposure in breastfed infants from mothers taking CBD and CBD-containing products. Cannabidiol concentrations in milk previously attained from data collected through an existing human milk research b...

Introduction Women-controlled HIV prevention technologies that overcome adherence challenges of available daily oral pre-exposure prophylaxis and give women a choice of options are urgently needed. Broadly neutralising monoclonal antibodies (bnAbs) administered passively may offer a valuable non-antiretroviral biological intervention for HIV preven...

Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and may have immunotherapeutic effects against HIV-1 reservoirs. We conducted a prospective clinical trial with two HIV-1 bNAbs (VRC01LS and 10-1074) in children (n = 25) who had previously initiated small-...

Pharmacokinetic (PK) studies in pregnant, postpartum, and breastfeeding people are critical to informing appropriate medication use and dosing. A key component of translating PK results in these complex populations into clinical practice involves the systematic review and interpretation of data by guideline panels, composed of clinicians, scientist...

Ethosuximide was identified as the optimal option for new-onset childhood absence epilepsy (CAE) in a randomized, two-phase dose escalation comparative effectiveness trial of ethosuximide, lamotrigine, and valproic acid. However, 47% of ethosuximide initial monotherapy participants experienced short-term treatment failure. This study aimed to chara...

Background and objective: High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C0) and steady-state area-under-curve (AUC0-24) targets is important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used to predict t...

Background: Despite its federally restricted status, cannabis is widely used medicinally and recreationally. The pharmacokinetics (PK) and central nervous system (CNS) effects of tetrahydrocannabinol (THC), the major psychoactive cannabinoid, are not well understood. The objective of this study was to develop a population PK model of inhaled THC,...

Background: People with HIV (PWH) are at increased risk for comorbidities and plasma IL-6 levels are among the most robust predictors of these outcomes. Tocilizumab (TCZ) blocks the receptor for IL-6, inhibiting functions of this cytokine. Methods: This was a 40-week placebo controlled, crossover trial (NCT02049437) where PWH on stable antiretro...

Background: Young women in sub-Saharan Africa continue to bear a high burden of HIV infection. Combination anti-HIV monoclonal antibodies are a potential HIV prevention technology that could overcome adherence challenges of daily oral pre-exposure prophylaxis. In this phase 1 clinical trial we aimed to determine the safety and pharmacokinetic prof...

Background: The diversity in the genomic landscape of advanced and metastatic tumors calls for combination therapies based on the genomic signature associated with each tumor. Determining safe and tolerable doses for novel combinations of oncology drugs is essential for a precision medicine approach, but can also require dose reductions. Trametini...

Background: Human monoclonal antibodies might offer an important new approach to reduce malaria morbidity and mortality. In the first two parts of a three-part clinical trial, the antimalarial monoclonal antibody CIS43LS conferred high protection against parasitaemia at doses of 20 mg/kg or 40 mg/kg administered intravenously followed by controlle...

Background: Fexofenadine is a recommended in vivo probe drug for phenotyping P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3 transporter activities. This study evaluated a limited sampling strategy using a population pharmacokinetic approach to estimate plasma fexofenadine exposure as an index of P-gp and OATP activit...

Pregnant individuals are at high risk for severe illness from COVID‐19 and there is an urgent need to identify safe and effective therapeutics for this population. Remdesivir (RDV) is a SARS‐CoV‐2 nucleotide analog RNA polymerase inhibitor. Limited RDV pharmacokinetic (PK) and safety data are available for pregnant women receiving RDV. The aims of...

Background: Early antiretroviral treatment (ART) improves outcomes in children, but few studies have comprehensively evaluated the impact of ART started from the first week of life. Methods: Children diagnosed with HIV within 96 hours of life were enrolled into the Early Infant Treatment Study in Botswana and followed on ART for 96 weeks. Nevira...

Long-acting antiretroviral products have the potential to transform human immunodeficiency virus (HIV) prevention and treatment approaches in pediatric populations. Broadly neutralizing antibodies and/or long-acting antiretroviral formulations by injection could dramatically improve provision of HIV prophylaxis and/or early treatment to newborns an...

Background: Treatment and prophylaxis options for neonatal HIV are limited. This study aimed to develop a population pharmacokinetic model to characterize the disposition of maraviroc in neonates to inform dosing regimens and expand available options. Methods: Using maraviroc concentrations from neonates who received either a single dose or mult...

Background: New approaches for the prevention and elimination of malaria, a leading cause of illness and death among infants and young children globally, are needed. Methods: We conducted a phase 1 clinical trial to assess the safety and pharmacokinetics of L9LS, a next-generation antimalarial monoclonal antibody, and its protective efficacy aga...

Although 23 antiretroviral drugs are approved for use in adults, only six are approved by regulatory authorities for use in term neonates born to women with HIV, with even fewer options for preterm neonates. A major hurdle for approvals is the delay in the generation of pharmacokinetic and safety data for antiretrovirals in neonates. The median tim...

Safe and effective paediatric formulations of the most promising antiretroviral drugs are crucial to advance the treatment and prevention of HIV in neonates, infants, children, and adolescents. The WHO Paediatric Drug Optimization for HIV (PADO-HIV) group brings together stakeholders and experts every 2–3 years to identify priority products and def...

Background: Broadly neutralizing monoclonal antibodies (bNAbs) suppress HIV-1 RNA and may deplete residual viral reservoirs. We evaluated the safety and pharmacokinetics (PK) of dual intravenous VRC01LS and 10-1074 in very early-treated children with HIV-1 on suppressive antiretroviral treatment (ART). Setting: Botswana. Methods: Children with...

Introduction: Treatment of HIV and tuberculosis (TB) co-infection leads to significant mortality in pediatric patients, and treatment can be challenging due to the clinically significant drug-drug interaction (DDI) between lopinavir/ritonavir (LPV/RTV) and rifampin. Doubling LPV/RTV doses results in insufficient lopinavir trough concentrations in...

Background: Tenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic data supporting the use of TAF during pregnancy are limited. Here, we report pharmacokinetic, safety, and birth outcomes with TAF 25 mg with a boosted protease inhibitor (PI) in pregnant women living with HIV (PWLH). Methods: IMPAACT P1026s was a mul...

Background: Isoniazid (INH) metabolism depends on the N-acetyl transferase 2 (NAT2) enzyme, whose maturation process remains unknown in low birth weight (LBW) and preterm infants. We aimed to assess INH exposure and safety in infants receiving oral tuberculosis prevention. Methods: This population pharmacokinetics (PK) analysis used INH and N-ac...

Introduction: Effective, long-acting prevention approaches are needed to reduce HIV incidence. We evaluated the safety and pharmacokinetics of VRC07-523LS and PGT121 administered subcutaneously alone and in combination as passive immunization for young women in South Africa. Methods: CAPRISA 012A was a randomised, double-blinded, placebo-control...

Urine drug testing (UDT) is a tool for monitoring drug use, including oxycodone. While variation in cytochrome P450 (CYP) genes is known to alter oxycodone metabolism, its impact on UDT results of oxycodone and its metabolites has not been well-studied. Here, multivariate analysis was performed on retrospective UDT results of 90,379 specimens colle...

OBJECTIVE To describe the frequency of use of tumor genomic profiling and functional ex vivo drug sensitivity testing in pediatric patients with hematologic malignancies at our institution, and to determine how the results affected treatment selection. METHODS A retrospective chart review was conducted to analyze the frequency of tumor genomic pro...

Clofazimine (CFZ) is a poorly soluble, weakly basic, small molecule antibiotic clinically used to treat leprosy and is now in clinical trials as a treatment for multidrug resistant tuberculosis and COVID-19. CFZ exhibits complex, context-dependent pharmacokinetics that are characterized by an increasing half-life in long term treatment regimens. Th...

Clofazimine (CFZ) is a weakly basic, small-molecule antibiotic used for the treatment of mycobacterial infections including leprosy and multidrug-resistant tuberculosis. Upon prolonged oral administration, CFZ precipitates and accumulates within macrophages throughout the host. To model the pharmacokinetics of CFZ, the volume of distribution (Vd) w...

Objective: Dosing efavirenz (EFV) in children less than 3 years of age is challenging due to large variability in drug levels. This study evaluated differences in pharmacokinetics (PK) with TB therapy, formulation, age, and CYP2B6 genotype. Design: PK data from three IMPAACT/PACTG studies (P382, P1021, P1070) for children initiating therapy less...

Background: Antiretroviral options for neonates (< 28 days of life) should be expanded. We evaluated the pharmacokinetics, safety, and acceptability of the '4-in-1' fixed-dose paediatric granule formulation of abacavir/lamivudine/lopinavir/ritonavir (30/15/40/10 mg) in neonates. Methods: The PETITE study is an ongoing phase I/II, open-label, sin...

Background No evidence-based optimal dosing guidance is available for abacavir liquid formulation use from birth. We used abacavir pharmacokinetic data from neonates and infants to determine an exact abacavir dosing strategy (mg/kg) for infants aged 0–3 months and to propose dosing by WHO weight band for neonates. Methods Abacavir pharmacokinetic...

Objectives To determine the safety, pharmacokinetics, and immunomodulatory effects of two- to six-weeks of anakinra in patients with acute KD Kawasaki disease with coronary artery aneurysms (CAA). Study design We performed a Phase I/IIa, dose-escalation study of anakinra (2-11 mg/kg/day) in 22 patients with acute KD Kawasaki disease with CAA. We m...

Background: This study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared to postpartum and in infant washout samples. Setting: A nonrandomized, open-label, parallel-group, multi-center prospective study of atazanavir and cobicistat pharmacokinetics in pregnant women with HIV and their children. Methods: Intensive s...

Background: Alterations in plasma protein concentrations in pregnant and postpartum individuals can influence antiretroviral (ARV) pharmacokinetics. Physiologically-based pharmacokinetic (PBPK) models can serve to inform drug dosing decisions in understudied populations. However, development of such models requires quantitative physiological inform...

Methicillin-resistant Staphylococcus aureus infections are a significant cause of morbidity and mortality in pediatric liver transplant (LT) recipients. Physiological changes following LT may affect vancomycin pharmacokinetics; however, appropriate dosing to achieve sufficient drug exposure (i.e., 24-h area under the concentration-time curve [AUC24...

Background: A knowledge gap exists for dolutegravir (DTG) pharmacokinetics and safety during the first 4 weeks of life, preventing safe and effective DTG use in neonates. Setting: Population pharmacokinetic (popPK) modeling and simulation was used to assess newborn DTG dosing requirements during the first days of life as a function of maternal D...

PurposeS-warfarin is used to phenotype cytochrome P450 (CYP) 2C9 activity. This study evaluated S-warfarin limited sampling strategy with a population pharmacokinetic (PK) approach to estimate CYP2C9 activity in healthy adults.Methods In 6 previously published studies, a single oral dose of warfarin 10 mg was administered alone or with a CYP2C9 ind...

Background Additional interventions are needed to reduce the morbidity and mortality caused by malaria. Methods We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with Plasmodium falciparum. Part A o...

Objectives: Long-acting reversible contraceptives are effective contraceptives for women with HIV, but there are limited data on etonogestrel implant and antiretroviral therapy pharmacokinetic drug-drug interactions. We evaluated etonogestrel/antiretroviral therapy drug-drug interactions, and the effects of etonogestrel on ritonavir-boosted-atazana...

What is known and objective: Tenofovir exposure is increased in non-pregnant adults when tenofovir disoproxil fumarate is coadministered with lopinavir/ritonavir. In pregnant women, tenofovir exposure is decreased. Our objective is to describe the effect of lopinavir/ritonavir on tenofovir pharmacokinetics during pregnancy. Methods: Data were co...

We address sampling design of population pharmacokinetics (popPK) experiments in the context of two phase 2b efficacy trials that evaluate the efficacy of VRC01 (vs. placebo) in reducing the rate of HIV infection among 4625 participants. Blood samples are collected at up to 22 study visits from all participants for immediate HIV diagnosis as the pr...

Background Meropenem is a broad-spectrum carbapenem antibiotic approved by the US Food and Drug Administration for use in pediatric patients, including treating complicated intra-abdominal infections in infants < 3 months of age. The impact of maturation in glomerular filtration rate and tubular secretion by renal transporters on meropenem pharmaco...

Background Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data.Objective The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learnin...

Background Perinatal HIV-1 continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs). Methods Extended half-life bNAb, VRC01LS, was administered subcutaneously (SC) at 80 mg/dose after birth to HIV-1-exposed, non-breastfed (Cohort 1, n=10) and...

Objective: To evaluate darunavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. Design: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United...

Pharmacokinetics of drugs can be affected by physiologic changes during pregnancy. Our aim was to assess the influence of covariates on tenofovir (TFV) pharmacokinetics in pregnant and postpartum women receiving tenofovir disoproxil fumarate (TDF). Population pharmacokinetic parameters estimates and the influence of covariates were assessed using n...

Cannabidiol (CBD), a non‐psychotropic phytocannabinoid from the Cannabis plant, is increasingly being pursued as a treatment for differing ailments. The bioavailability and pharmacokinetics of CBD are not well understood, and proper dosing schemes have not been adequately developed for its clinical use. CBD is a lipophilic molecule and exhibits low...

Introduction: New HIV prevention strategies are urgently required. The discovery of broadly neutralising antibodies (bNAbs) has provided the opportunity to evaluate passive immunisation as a potential prevention strategy and facilitate vaccine development. Since 2014, several bNAbs have been isolated from a clade C-infected South African donor, CA...

Objective: To evaluate the pharmacokinetics of tenofovir alafenamide (TAF) 10 mg with cobicistat and 25 mg without boosting in pregnant and postpartum women with HIV and to characterize TAF placental transfer and infant washout pharmacokinetics. Design: Open-label, multicenter phase IV prospective study of TAF pharmacokinetics during pregnancy, po...

Background With increasing intention to treat HIV as early as possible, evidence to confirm the safety and therapeutic drug concentrations of a nevirapine-based antiretroviral regimen in the early neonatal period is needed. This study aims to establish dosing of nevirapine for very early treatment of HIV-exposed neonates at high risk of HIV acquisi...

Information on the extent of drug exposure to mothers and infants during pregnancy and lactation normally becomes available years after regulatory approval of a drug. Clinicians face knowledge gaps on drug selection and dosing in pregnancy and infant exposure during breastfeeding. Physiological changes during pregnancy often result in lower drug ex...

Background: Current pediatric International Society for Peritoneal Dialysis guidelines for initial treatment of peritoneal dialysis (PD)-associated peritonitis suggest either monotherapy with cefepime or double therapy with first-generation cephalosporin or glycopeptide and ceftazidime or aminoglycoside. When using vancomycin, the intraperitoneal...

Background: Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for preconceptional treatment to reduce parasitic load. The fear of treatme...

An estimated 40 million women of reproductive age are infected with one of three species of the waterborne parasite Schistosoma ( S. ) spp. Treatment with praziquantel (PZQ) via mass drug administration (MDA) campaigns is the mainstay of schistosomiasis control for populations living in endemic areas. The World Health Organization recommends that p...

VRC01 is a first‐in‐class, potent, broadly neutralizing antibody that targets the CD4 binding site of gp120 on HIV‐1 viruses, and is under development as a novel HIV therapeutic. This study utilized population pharmacokinetic modeling to characterize VRC01 pharmacokinetics to guide dosing selection for ongoing phase 2 clinical trials in pediatric p...

OBJECTIVES The objectives of this study were to 1) define extent and potential clinical impact of increased or decreased renal elimination of meropenem in children with sepsis, based on analysis of renal function during the first 2 days of PICU stay; and 2) estimate the risk of subtherapeutic meropenem exposure attributable to increased renal clear...

Background Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for preconceptional treatment to reduce parasitic load. The fear of treatment...

Objectives Pharmacokinetic parameters can change significantly during extracorporeal membrane oxygenation (ECMO) and continuous hemodialysis. The present case report describes the pharmacokinetics of a three-hour meropenem infusion in an infantile anuric patient on ECMO with continuous hemodialysis. Case A 19-month-old female patient with asplenia...

The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady-state during the second and third trimesters of pregnancy and postpartum. Plasma concentration...

This clinical trial evaluated the independent and combined effects of a tricyclic antidepressant (desipramine) and cognitive behavioral therapy (CBT) for chronic back pain relative to an active placebo treatment. Participants (n=142) were patients experiencing daily chronic back pain at an intensity of ≥4/10 who were randomized to a single center,...

Background: Early antiretroviral treatment (ART) is recommended for HIV-infected infants. However, few antiretroviral options are available for neonates. Methods: The Early Infant Treatment Study in Botswana tested HIV-exposed infants using DNA PCR within 96 hours of birth, and HIV-infected infants started nevirapine (NVP) 6mg/kg BID, zidovudine...

Background: This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum. Methods: Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r...

Purpose High-dose methotrexate (HD-MTX) is widely used in pediatric and adult oncology treatment regimens. This study aimed to develop a population pharmacokinetic model to characterize pediatric and adult MTX exposure across various disease types and dosing regimens, and to evaluate exposure–toxicity relationships. Methods MTX pharmacokinetic dat...

Background: Population modeling and simulations can be used to facilitate the conduct of phase I studies to develop safe and effective dosing regimens in neonates. Setting: P1110 is an international, multicenter trial to determine safe and effective raltegravir doses in neonates at risk for HIV infection. Methods: P1110 used a 2-cohort adaptiv...

Background: Deoxycytidine kinase (dCK) is an essential enzyme for production of nucleotides via the salvage pathway; DI-87 is a novel dCK inhibitor in preclinical development for use in anticancer therapy. The current study utilizes PET imaging to evaluate PK-PD relationships and to determine optimal dosing of the drug. Methods: NSG mice bearing...

Background: While mother-to-child HIV transmission has dramatically decreased with maternal antiretroviral therapy, breast milk transmission accounts for most of the 180,000 new infant HIV infections annually. Broadly neutralizing antibodies (bNAb) may further reduce transmission. Methods: A Phase I safety and pharmacokinetic study was conducted...

Purpose To characterize the effects of disease type and clinical characteristics on the pharmacokinetics of siltuximab, an IL-6 inhibiting monoclonal antibody. Methods Siltuximab pharmacokinetic data were combined from seven phase I/II clinical trials. A population pharmacokinetic model was developed to characterize changes in siltuximab dispositi...

Background: Acute seizures are common in pediatric cerebral malaria (CM), but usual care with phenobarbital risks respiratory suppression. We undertook studies of enteral levetiracetam (eLVT) to evaluate pharmacokinetics (PK), safety and efficacy including an open-label, randomized controlled trial (RCT) comparing eLVT to phenobarbital. Methods:...

We report on an 8‐year‐old girl with Wilson disease who developed three episodes of peritonitis due to extended‐spectrum beta‐lactamase‐producing Escherichia coli after liver transplantation. Massive ascites were thought to account for low meropenem concentrations with standard dosing. Extending the infusion achieved higher troughs, greater time ab...

Pregnancy is associated with physiological changes that may impact drug pharmacokinetics (PK). The goals of this study were to build maternal‐fetal physiologically based pharmacokinetic (PBPK) models for acyclovir and emtricitabine, 2 anti(retro)viral drugs with active renal net secretion, and to (1) evaluate the predicted maternal PK at different...

Background: CYP2B6 516 genotype-directed dosing improves efavirenz (EFV) exposures in HIV-infected children younger than 36 months, but such data are lacking in those with tuberculosis (TB) coinfection. Methods: Phase I, 24-week safety and pharmacokinetic (PK) study of EFV in HIV-infected children aged 3 to <36 months, with or without TB. CYP2B6...

Background: Human monoclonal antibodies that potently and broadly neutralise HIV-1 are under development to prevent and treat HIV-1 infection. In this phase 1 clinical trial we aimed to determine the safety, tolerability, and pharmacokinetic profile of the broadly neutralising monoclonal antibody VRC07-523LS, an engineered variant of VRC01 that ta...

Background: The only antiretrovirals (ARV) approved to treat HIV- exposed infants below 37 weeks gestational age (GA) are nevirapine (NVP), zidovudine and lamivudine. The NVP concentration target for treatment (3 mcg/mL) is 30-fold that for prophylaxis (0.1 mcg/mL). Preterm infants have reduced NVP clearance compared to term infants; doses of 4 mg/...