scholarly journals O06 Methadone dosing strategies in preterm neonates can be simplified

2019 ◽  
Vol 104 (6) ◽  
pp. e3.1-e3
Author(s):  
T van Donge ◽  
S Samiee-Zafarghandy ◽  
M Pfister ◽  
G Koch ◽  
M Kalani ◽  
...  
Keyword(s):  
Gestational Age ◽  
Clinical Investigation ◽  
Withdrawal Symptoms ◽  
Preterm Neonates ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Open Label ◽  
Elimination Kinetics ◽  
Dosing Strategies ◽  
Dosing Strategy

AimsA dramatic increase in newborn infants with neonatal abstinence syndrome has been observed and these neonates are frequently treated with complex methadone dosing schemes to control their withdrawal symptoms. Despite its abundant use, hardly any data on the pharmacokinetics of methadone is available in preterm neonates. Therefore we investigated developmental pharmacokinetics of methadone and evaluated current dosing strategies and possible simplification in this vulnerable population.MethodsA single center open-label prospective study was performed to collect pharmacokinetic data after a single oral dose of methadone in preterm neonates. A population pharmacokinetic model was built to characterize developmental pharmacokinetics of methadone and to assess the effects of weight and age on clearance and volume of distribution. In addition, simulation techniques were applied to evaluate reported dosing scenarios, investigate methadone exposure levels and examine the feasibility of simplified dosing recommendations.ResultsIn total, 121 methadone concentrations were collected from 31 preterm neonates. The median weight and gestational age amounted 1.6 kg and 32 weeks, respectively. A one-compartment model with first order absorption and elimination kinetics best described the data for (R)- and (S)-methadone. Clearance was observed to be higher for the (R)-enantiomer as compared to the (S)-enantiomer (0.244 versus 0.167 L/h). Target exposures, based on simulations, can be maintained with a simplified dosing strategy during the first four days of treatment. It is therefore questionable if there is a need for the currently used more extended dosing regimen of methadone in neonates.conclusionsThis clinical investigation demonstrates that the clearance of methadone increases with advancing gestational age and higher clearance values and volumes of distribution can be observed for (R)-methadone as compared to (S)-methadone in preterm neonates. Simulations that account for developmental pharmacokinetics indicate that a simplified methadone dosing strategy can maintain target exposure to control withdrawal symptoms in preterm neonates.Disclosure(s)Nothing to disclose

A Systematic Review On Different Prothrombin Complex Concentrate Strategies To Reverse Vitamin K Antagonist Therapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3639-3639
Author(s):  
Nakisa Khorsand ◽  
Hilde A.M. Kooistra ◽  
Reinier M. van Hest ◽  
Pharm D ◽  
Nic J.G.M. Veeger ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Outcome ◽  
Quality Assessment ◽  
Vitamin K ◽  
Vitamin K Antagonist ◽  
Factor Ix ◽  
Fixed Dose ◽  
Open Label ◽  
Dosing Strategies ◽  
Dosing Strategy

Abstract Management of patients with a major bleed while on vitamin K antagonist (VKA) is a common clinical challenge. Prothrombin Complex Concentrates (PCC) provide a rapid reversal of VKA induced coagulopathy. The aim of this systematic review is to describe the currently used PCC strategies and to present their efficacy in terms of target INR achievement and clinical outcome. MEDLINE and EMBASE databases were searched for studies reporting the use of PCC for emergency reversal of VKA therapy. Additional inclusion criteria were the reporting of PCC dosing strategy, data on target INR or any clinical outcome or safety parameters, prospective patient enrollment, and a full text publication. All PCC studies in non-VKA patients, case-reports (N<5), duplicates, retrospective studies, and studies on activated PCC were excluded. The quality of selected studies was evaluated using two quality assessment tools which are described by Downs (J Epidemiol Community Health, 1998), and Thomas (McMaster University, 2008). A total of 27 studies was included in which the majority was single cohort (N=18, 67%), open label (N=27, 100%), and/or nonrandomized (N=23, 85%). The total number of included patients was 2410, ranging from 5 to 686 patients per study. One of the included studies was scored as having a strong, 12 a moderate and 14 a weak design. The median quality assessment score was 16 out of 26 [range 10-22]. A large heterogeneity in study parameters was observed including 6 different primary endpoints with 12 different definitions. Fifteen PCC protocols were identified in which the PCC dose ranged from 8 to 50 IU of factor IX/kg or a fixed dose protocol of 200, 500, 1000, or 1500 IU of factor IX/patient. These dosing strategies were based on five principals, namely based on bodyweight (BW), bodyweight and initial INR (BW+INRi), bodyweight and initial INR and target INR (BW+INRi+INRt), individual doctors decision (doctor) or a fixed dose (fixed). The actual infused dosage is depicted in figure 1. Evaluating the used dosing strategy, target INR was reached in 86%, 81%, 78% and 75% of patient in BW, BW+INRi, BW+INRi+INRt and fixed, respectively and was lower (55%) in doctor strategy. Of note, results of the doctor strategy are based on two studies. Clinical outcome was positive for 75%, 93%, 85%, 88% and 67% of patients in strategy BW, BW+INRi, BW+INRi+INRt, fixed, and doctor strategy respectively. Of note, only one study reported on the clinical outcome in the BW+INRi strategy and two in doctor strategy. While our review shows a great diversity on PCC dosing strategies among published data, the same applies to current PCC guidelines in which the ACCP leaves the dosing to the discretion of the physician, the French guidelines recommend a bodyweight adjusted dosing regardless of the INR, the Canadian guidelines recommend three different fixed doses stratified by initial INR, and the Australian guidelines recommend a range of bodyweight adjusted doses from which the physician should decide. Apart from the different dosing strategies, considerable heterogeneity in assessing the impact of PCC treatment was noticed indicating the lack of consensus regarding different aspects of emergency reversal of VKA treatment e.g. optimal target INR, clinical outcome definition. Furthermore, PCC is predominantly studied in small, single-arm and open label settings using the INR to measure its effect rather than clinical outcome. In addition, results from our quality assessment showed that most study designs were at most moderately robust. Evidence gained from the included studies should therefore be interpreted with caution. In conclusion, this review shows that the worst results are reported when a predefined dosing protocol is absent (doctors strategy), while with the use of any treatment protocol good outcome results of PCC treatment are obtained (target INR reached ³ 75%, positive clinical response ³ 75%). A fixed dose strategy seems to be the most simple treatment, with a high potential for optimal clinical outcome while the lowest PCC dosages are infused. Good quality studies with consistent endpoints are needed to guide clinical use. Actual median dose infused in each study(arm). Dots represent the included studies(cohorts) with large, average and small amount of included patients Disclosures: Khorsand: Sanquin BV, Amsterdam: Research Funding.

Novel strategy to personalise use of ibuprofen for closure of patent ductus arteriosus in preterm neonates

2021 ◽  
pp. archdischild-2020-321381
Author(s):  
Samira Samiee-Zafarghandy ◽  
Tamara van Donge ◽  
Gerhard Fusch ◽  
Marc Pfister ◽  
George Jacob ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Gestational Age ◽  
Ductus Arteriosus ◽  
Plasma Concentrations ◽  
Preterm Neonates ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Target Exposure ◽  
Patent Ductus

ObjectiveExploration of a novel therapeutic drug monitoring (TDM) strategy to personalise use of ibuprofen for closure of patent ductus arteriosus (PDA) in preterm neonates.DesignProspective, single-centre, open-label, pharmacokinetics study in preterm neonates.SettingNeonatal intensive care unit at McMaster Children’s Hospital.PatientsNeonates with a gestational age ≤28+6 weeks treated with oral ibuprofen for closure of a PDA.MethodsPopulation pharmacokinetic parameters, concentration-time profiles and exposure metrics were obtained using pharmacometric modelling and simulation.Main outcome measureAssociation between ibuprofen plasma concentrations measured at various sampling time points on the first day of treatment and attainment of the target exposure over the first 3 days of treatment (AUC0–72h >900 mg·hour/L).ResultsTwenty-three preterm neonates (median birth weight 780 g and gestational age 25.9 weeks) were included, yielding 155 plasma ibuprofen plasma samples. Starting from 8 hours’ postdose on the first day, a strong correlation between ibuprofen concentrations and AUC0–72h was observed. At 8 hours after the first dose, an ibuprofen concentration >20.5 mg/L was associated with a 90% probability of reaching the target exposure.ConclusionWe designed a novel and practical TDM strategy and have shown that the chance of reaching the target exposure (AUC0–72h >900 mg·hour/L) can be predicted with a single sample collection on the first day of treatment. This newly acquired knowledge can be leveraged to personalise ibuprofen dosing regimens and improve the efficacy of ibuprofen use for pharmacological closure of a PDA.

scholarly journals Population Pharmacokinetics of Vancomycin in the Pediatric Cardiac Surgical Population

2019 ◽  
Vol 24 (2) ◽  
pp. 107-116 ◽  
Author(s):  
Brady S. Moffett ◽  
Karla Resendiz ◽  
Jennifer Morris ◽  
Ayse Akcan-Arikan ◽  
Paul A. Checchia
Keyword(s):  
Serum Concentration ◽  
Creatinine Clearance ◽  
Cardiac Surgical Procedures ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Population Pharmacokinetic Study ◽  
Postmenstrual Age ◽  
Dosing Strategy

OBJECTIVE Vancomycin is often used in the pediatric cardiac surgical population, but few pharmacokinetic data are available to guide dosing. METHODS A retrospective, population pharmacokinetic study was performed for patients &lt;19 years of age initiated on vancomycin after cardiac surgery in the cardiac intensive care unit from 2011–2016 in our institution. Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM. Simulation was performed to determine a dosing strategy that most frequently obtained an AUC0–24:MIC (minimum inhibitory concentration) ratio of &gt;400. RESULTS A total of 261 patients (281 cardiac surgical procedures, cardiopulmonary bypass 82.3%) met inclusion criteria (60.1% male, median age 0.31 [IQR, 0.07–0.77] years). Vancomycin (14.5 ± 1.7 mg/kg/dose) was administered at median postoperative day 9 (IQR, 4–14), with a mean serum concentration of 11.5 ± 5.5 mg/L at 8.9 ± 3.8 hours after a dose. Population pharmacokinetic analysis demonstrated that a 1-compartment proportional error model with allometrically scaled weight best fit the data, with creatinine clearance and postmenstrual age as significant covariates. Simulation identified that a dosing regimen of 20 mg/kg/dose every 8 hours was most likely to achieve an AUC0–24:MIC ratio &gt; 400 at a mean trough serum concentration of 12.9 ± 3.2 mg/L. CONCLUSIONS Vancomycin dosing in the postoperative pediatric cardiac surgical population should incorporate postmenstrual age and creatinine clearance. A vancomycin dose of 20 mg/kg every 8 hours is a reasonable empiric strategy.

scholarly journals P62 Population pharmacokinetic study of aminophylline in Indian preterm neonates (≤34weeks) with apnoea; a longitudinal observational study

2019 ◽  
Vol 104 (6) ◽  
pp. e43.1-e43
Author(s):  
S M ◽  
L Lewis ◽  
S Mallayasamy
Keyword(s):  
Gestational Age ◽  
Dosage Regimen ◽  
Drug Evaluation ◽  
Controlled Trial ◽  
Significant Proportion ◽  
Visual Predictive Check ◽  
Preterm Neonates ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies ◽  
List Type

BackgroundCurrent dosage regimen of aminophylline is similar in both Appropriate for Gestational Age (AGA) and Small for Gestational Age (SGA) preterm neonates.1 In contrast with AGA babies, SGA babies handle drugs in different way. However, developing countries like India has significant proportion of Growth Restricted/SGA babies. Hence, there is a need to develop appropriate dosage regimen in this population. Objective of the current study was set to develop and qualify the Population-Pharmacokinetic (PPK) model for aminophylline in premature neonates in Indian population.2MethodsAminophylline-treated neonates with IV loading dose of 5 mg/kg followed by maintenance dose of 1.5 or 2 mg/kg 8th hourly for Apnoea of Prematurity (AOP) were included. Any other conditions for secondary causes were excluded. Blood samples were collected by adopting sparse sample scheme and estimated by LCMS-MS. PPK model was developed with appropriate covariates.3 Data was analysed by NONMEM vesion 7.3. Non-parametric bootstrap procedure and Visual Predictive Check (VPC) was used to qualify the developed model.ResultsOne compartment, first-order structured model was fitted to the dataset containing 454 observations from 107 neonates. PPK parameters were represented as model estimated values and variability was depicted as% Co-efficient of variation (%CV). Typical population value of CL was 0.011 L/hour with inter-individual variability (IIV) of 59% and V was 0.332 (L/kg) with 31% IIV. Residual error was found to be 19%. Only postnatal age (PNA) had significant effect on V which was assessed by forward addition and backword elimination regression model.ConclusionAGA and SGA had no influence on PK parameters. However, PNA showed to have significant influence on V. Developed nomogram based on the qualified model may be effective and safe for aminophylline therapy in preterm neonates with apnoea.ReferencesShivakumar M, Jayashree P, Najih M, Lewis LES, Bhat Y R, Kamath A, et al. Comparative Efficacy and Safety of Caffeine and Aminophylline for Apnea of Prematurity in Preterm (≤34 weeks) Neonates: A Randomized Controlled Trial. Indian Pediatr 2017 Apr 15;54(4):279–83.U S Department of Health and Human Services, FDA, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER): Guidance for Industry Population pharmacokinetics; 1991; Feb CP1, 35 pages.Ette EI, Sun H, Ludden TM, Balanced designs in longitudinal Population Pharmacokinetic studies. Journal of Clinical Pharmacology 1998 May; 38(5):417–423.Disclosure(s)Nothing to disclose

scholarly journals Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial

2021 ◽  
Vol 6 ◽  
pp. 161
Author(s):  
Peter Olupot-Olupot ◽  
William Okiror ◽  
Hellen Mnjalla ◽  
Rita Muhindo ◽  
Sophie Uyoga ◽  
...  
Keyword(s):  
Severe Malaria ◽  
Controlled Trial ◽  
Antimicrobial Treatment ◽  
Phase Iii ◽  
Current Evidence ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Open Label ◽  
Post Discharge ◽  
African Children

Background: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. Methods: A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection. Discussion: We plan to study azithromycin because of its favourable microbiological spectrum, its inherent antimalarial and immunomodulatory properties and dosing and safety profile. This study will generate new data to inform the design and sample size for definitive Phase III trial evaluation. Registration: ISRCTN49726849 (27th October 2017).

scholarly journals Adjunctive Perampanel Oral Suspension in Pediatric Patients From ≥2 to <12 Years of Age With Epilepsy: Pharmacokinetics, Safety, Tolerability, and Efficacy

2019 ◽  
Vol 34 (5) ◽  
pp. 284-294 ◽  
Author(s):  
J. Ben Renfroe ◽  
Mark Mintz ◽  
Ronald Davis ◽  
Jose Ferreira ◽  
Sharon Dispoto ◽  
...  
Keyword(s):  
Population Pharmacokinetic Analysis ◽  
Oral Suspension ◽  
Extension Phase ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Open Label ◽  
Core Study ◽  
Adults And Children

Study 232, an open-label pilot study with an extension phase, evaluated the pharmacokinetics and preliminary safety/tolerability and efficacy of adjunctive perampanel oral suspension (≤0.18 mg/kg/d) in epilepsy patients aged ≥2 to <12 years. Patients were grouped into cohorts 1 (aged ≥7 to <12 years) and 2 (aged ≥2 to <7 years). The Core Study included pretreatment (≤2 weeks) and treatment phases (7-week titration; 4-week maintenance; 4-week follow-up [for those not entering the extension]). The extension phase consisted of 41-week maintenance and 4-week follow-up periods. Pharmacokinetic data were pooled with adolescent pharmacokinetic data from phase II/III studies. Population pharmacokinetic analysis showed that perampanel pharmacokinetics was independent of age, weight, or liver function, suggesting age- or weight-based dosing is not required and that the same dose can be given to adults and children to achieve exposures shown to be efficacious. Perampanel was well tolerated and efficacious for ≤52 weeks.

scholarly journals Rapidly maturing fentanyl clearance in preterm neonates

2019 ◽  
Vol 104 (6) ◽  
pp. F598-F603 ◽  
Author(s):  
Swantje Völler ◽  
Robert B Flint ◽  
Peter Andriessen ◽  
Karel Allegaert ◽  
Luc J I Zimmermann ◽  
...  
Keyword(s):  
Gestational Age ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Preterm Neonates ◽  
Population Pharmacokinetic ◽  
Additional Information ◽  
Two Compartment Model ◽  
Require Dose ◽  
Preterm Newborns ◽  
Pharmacodynamic Data

BackgroundFentanyl is frequently used off-label in preterm newborns. Due to very limited pharmacokinetic and pharmacodynamic data, fentanyl dosing is mostly based on bodyweight. This study describes the maturation of the pharmacokinetics in preterm neonates born before 32 weeks of gestation.Methods442 plasma samples from 98 preterm neonates (median gestational age: 26.9 (range 23.9–31.9) weeks, postnatal age: 3 (range 0–68) days, bodyweight 1.00 (range 0.39–2.37) kg) were collected in an opportunistic trial and fentanyl plasma levels were determined. NONMEM V.7.3 was used to develop a population pharmacokinetic model and to perform simulations.ResultsFentanyl pharmacokinetics was best described by a two-compartment model. A pronounced non-linear influence of postnatal and gestational age on clearance was identified. Clearance (L/hour/kg) increased threefold, 1.3-fold and 1.01-fold in the first, second and third weeks of life, respectively. In addition, clearance (L/hour/kg) was 1.4-fold and 1.7-fold higher in case of a gestational age of 28 and 31 weeks, respectively, compared with 25 weeks. Volume of distribution changed linearly with bodyweight and was 8.7 L/kg. To achieve similar exposure across the entire population, a continuous infusion (µg/kg/hour) dose should be reduced by 50% and 25% in preterm neonates with a postnatal age of 0–4 days and 5–9 days in comparison to 10 days and older.ConclusionBecause of low clearance, bodyweight-based dosages may result in fentanyl accumulation in neonates with the lowest postnatal and gestational ages which may require dose reduction. Together with additional information on the pharmacodynamics, the results of this study can be used to guide dosing.

Acute kidney injury in preterm neonates with ≤30 weeks of gestational age and its risk factors

2019 ◽  
Vol 71 (5) ◽  
Author(s):  
Rita Ladeiras ◽  
Filipa Flor-De-Lima ◽  
Henrique Soares ◽  
Bárbara Oliveira ◽  
Hercília Guimarães
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Gestational Age ◽  
Kidney Injury ◽  
Preterm Neonates

scholarly journals TeleNeurological evaluation and Support for the Emergency Department (TeleNS-ED): protocol for an open-label clinical trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e048293
Author(s):  
Jessica Mandrioli ◽  
Mario Santangelo ◽  
Antonio Luciani ◽  
Stefano Toscani ◽  
Elisabetta Zucchi ◽  
...  
Keyword(s):  
Emergency Department ◽  
Clinical Investigation ◽  
Neurological Diseases ◽  
Medical Personnel ◽  
Primary Objective ◽  
Control Group ◽  
National Guidelines ◽  
Open Label ◽  
Time Saving ◽  
Hospital Networks

IntroductionThe COVID-19 pandemic compelled health systems to protect patients and medical personnel during transit in hospitals by minimising transfers, prompting the use of telehealth systems. In the field of neurology, telemedicine has been used in emergency settings for acute stroke management between spoke and hub hospital networks, where good outcomes have been achieved. However, data on the use of telemedicine in non-stroke acute neurological conditions accessing the emergency department (ED) are currently missing.Methods and analysesThis is an interventional, open-label trial on the use of teleconsultation in the ED for neurological diseases other than stroke. The study aims to develop a remote consultancy system (TeleNeurological Evaluation and Support, TeleNS) for patients with acute neurological symptoms referred to hospital facilities without a 24-hour availability of a neurologist consultant (spoke hospitals). The study population will include 100 ED patients referred to two spoke hospitals in 6 months, who will be asked to perform teleconsultation instead of inperson visits. As a control group, retrospectively available data from patients admitted to the ED of spoke hospitals during the same time period over the last 2 years will be evaluated. The primary objective is to assess whether a TeleNS for the ED guarantees a faster but qualitatively non-inferior diagnostic/therapeutic work-up if compared with inperson examination, assuring the availability of all the necessary examinations and treatments with consistent time-saving.Ethics and disseminationThe trial was designed following the national guidelines on clinical investigation on telemedicine provided by the Italian Ministry of Health and according to the Standard Protocol Items for Randomized Trials statement guidelines. This research protocol was approved by Comitato Etico Area Vasta Emilia Nord in September 2020 (number/identification: 942/2020/DISP/AOUMO SIRER ID 805) and was written without patient involvement. Patients’ associations will be involved in the dissemination of study design and results. The results of the study will be presented during scientific symposia or published in scientific journals.Trial registration numberNCT04611295.

scholarly journals Pharmacokinetic and safety study of co-administration of albendazole, diethylcarbamazine, Ivermectin and azithromycin for the integrated treatment of Neglected Tropical Diseases

2020 ◽  
Author(s):  
Lucy N John ◽  
Catherine Bjerum ◽  
Pere Millat Martinez ◽  
Rhoda Likia ◽  
Linda Silus ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Large Scale ◽  
Neglected Tropical Diseases ◽  
Pharmacokinetic Interaction ◽  
Integrated Treatment ◽  
Secondary Outcome ◽  
Pharmacokinetic Data ◽  
Tropical Diseases ◽  
Open Label ◽  
Significant Difference

Abstract Background Pharmacokinetic data are a pre-requisite to integrated implementation of large-scale mass drug administration (MDA) for neglected tropical diseases (NTDs). We investigated the safety and drug interactions of a combination of azithromycin (AZI) targeting yaws and trachoma, with the newly approved ivermectin, albendazole, diethylcarbamazine (IDA) regime for Lymphatic Filariasis. Methodology An open-label, randomized, 3-arm pharmacokinetic interaction study in adult volunteers was carried out in Lihir Island, Papua New Guinea. Healthy adult participants were recruited and randomized to (I) IDA alone, (II) IDA combined with AZI, (III) AZI alone. The primary outcome was lack of a clinically relevant drug interaction. The secondary outcome was the overall difference in the proportion of AEs between treatment arms. Results Thirty-seven participants, eighteen men and nineteen women, were randomized and completed the study. There were no significant drug-drug interactions between the study arms. The GMR of Cmax, AUC0–t, and AUC0–∞ for IVM, DEC, ALB-SOX, and AZI were within the range of 80–125% (GMR for AUC0–∞ for IVM, 87.9; DEC, 92.9; ALB-SOX, 100.0; and AZI, 100.1). There was no significant difference in the frequency of AEs across study arms (AZI and IDA alone arms 9/12 (75%), co-administration arm 12/13 (92%); p = 0.44). All AEs were grade 1 and self-limiting. Conclusions Co-administration of AZI with IDA did not show evidence of significant drug-interactions. There were no serious AEs in any of the study arms. Our data support further evaluation of the safety of integrated MDA for NTDs. Clinical Trials Registration. NCT03664063

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