Physicochemical compatibility of caffeine citrate and caffeine base injections with parenteral medications used in neonatal intensive care settings.

Purpose: To investigate the physicochemical compatibility of caffeine citrate and caffeine base injections with 43 secondary intravenous (IV) drugs used in Neonatal Intensive Care Unit (NICU) settings.

Methods: Caffeine citrate (20 mg/mL or 10 mg/mL) or caffeine base injection (10 mg/mL) were mixed in a volume ratio of 1:1 with the secondary drug solution to simulate Y-site co-administration procedures in NICUs. Physical compatibility was evaluated based on visual observation for 2 h, against a black and white background and under polarised light, for changes in colour, precipitation, haze and evolution of gas.

The Physicochemical Compatibility of Sildenafil Injection with Parenteral Medications Used in Neonatal Intensive Care Settings.

Sildenafil is used to treat pulmonary hypertension in neonatal intensive care unit (NICU) settings. As multiple intravenous (IV) medications are co-administered in NICU settings, we sought to investigate the physicochemical compatibility of sildenafil with a range of IV drugs. Sildenafil 600 mcg/mL or 60 mcg/mL was mixed 1:1 with the secondary drug solution to simulate Y-site co-administration procedures.

Could late-latent syphilis be treated with a single subcutaneous infusion of long-acting penicillin?

Syphilis is an important global health threat and little has changed in its treatment since the mid-20th century. For late-latent or syphilis infection of unknown duration, the standard treatment of multiple intramuscular injections of benzathine penicillin G (BPG) are associated with significant pain and distress to clients and caregivers, negatively impacting on treatment completion. Based on pharmacokinetic modelling from a Phase I study of subcutaneous infusion of high dose BPG (SCIP), we present its feasibility, safety and tolerability for treatment of syphilis in a single infusion.

Development of a pharmaceutical science systematic review process using a semi-automated machine learning tool: Intravenous drug compatibility in the neonatal intensive care setting.

Our objective was to establish and test a machine learning-based screening process that would be applicable to systematic reviews in pharmaceutical sciences. We used the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research type) model, a broad search strategy, and a machine learning tool (Research Screener) to identify relevant references related to y-site compatibility of 95 intravenous drugs used in neonatal intensive care settings. Two independent reviewers conducted pilot studies, including manual screening and evaluation of Research Screener, and used the kappa-coefficient for inter-reviewer reliability.

Subcutaneous infusion of high-dose benzathine penicillin G is safe, tolerable, and suitable for less-frequent dosing for rheumatic heart disease secondary prophylaxis: a phase 1 open-label population pharmacokinetic study.

Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine penicillin G [BPG; 1.2 MU (900 mg)] injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is suboptimal.

The effect and control of malaria in pregnancy and lactating women in the Asia-Pacific region.

Half of all pregnancies at risk of malaria worldwide occur in the Asia-Pacific region, where Plasmodium falciparum and Plasmodium vivax co-exist. Despite substantial reductions in transmission, malaria remains an important cause of adverse health outcomes for mothers and offspring, including pre-eclampsia. Malaria transmission is heterogeneous, and infections are commonly subpatent and asymptomatic.

Short-course, high-dose primaquine regimens for the treatment of liver-stage vivax malaria in children.

Objectives: To assess the pharmacokinetics, safety, and tolerability of two high-dose, short-course primaquine (PQ) regimens compared with standard care in children with Plasmodium vivax infections.

Methods: We performed an open-label pediatric dose-escalation study in Madang, Papua New Guinea (Clinicaltrials.gov NCT02364583).

Ultra-short course, high-dose primaquine to prevent Plasmodium vivax infection following uncomplicated pediatric malaria: A randomized, open-label, non-inferiority trial of early versus delayed treatment.

Objectives: We aimed to assess safety, tolerability, and Plasmodium vivax relapse rates of ultra-short course (3.5 days) high-dose (1 mg/kg twice daily) primaquine (PQ) for uncomplicated malaria because of any Plasmodium species in children randomized to early- or delayed treatment.

Methods: Children aged 0.

Piperaquine Pharmacokinetic and Pharmacodynamic Profiles in Healthy Volunteers of Papua New Guinea after Administration of Three-Monthly Doses of Dihydroartemisinin-Piperaquine.

Mass drug administration (MDA) with monthly dihydroartemisinin-piperaquine (DHA-PQP) appears useful in malaria control and elimination strategies. Determining the relationship between consecutive piperaquine phosphate (PQP) exposure and its impact on QT interval prolongation is a key safety consideration for MDA campaigns. Healthy volunteers from Papua New Guinea received a 3-day course of DHA-PQP (2.

The effect of sickle cell genotype on the pharmacokinetic properties of artemether-lumefantrine in Tanzanian children.

Since there are inconsistent data relating to the effect of haemoglobinopathies on disposition of artemisinin antimalarial combination therapy, and none in sickle cell trait (SCT) or sickle cell disease (SCD), the aim of this study was to characterize the pharmacokinetic properties of artemether-lumefantrine (ARM-LUM) in children with SCD/SCT. Thirty-eight Tanzanian children aged 5-10 years with normal (haemoglobin AA; n = 12), heterozygous (haemoglobin AS; n = 14) or homozygous (haemoglobin SS; n = 12) sickle genotypes received six ARM-LUM doses (1.7 mg/kg plus 10 mg/kg, respectively) over 3 days.

Antimalarials for children with Plasmodium vivax infection: Current status, challenges, and research priorities.

The aim of this narrative review is to summarise efficacy and pharmacokinetic data for Plasmodium vivax in children. The burden of P. vivax malaria in children continues to remain a significant public health issue, and the need for improved treatment regimens for this vulnerable population is critical.

The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network.

Background: There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial.

Methods And Findings: A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P.

Population Pharmacokinetic Study of Ceftriaxone in Elderly Patients, Using Cystatin C-Based Estimates of Renal Function To Account for Frailty.

Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies. A prospective population pharmacokinetic study of ceftriaxone in adults over 65 years old was undertaken. Dried blood spots collected at baseline (predose) and 0.

Updated pharmacokinetic considerations for the use of antimalarial drugs in pregnant women.

Introduction: The association between pregnancy and altered drug pharmacokinetic (PK) properties is acknowledged, as is its impact on drug plasma concentrations and thus therapeutic efficacy. However, there have been few robust PK studies of antimalarial use in pregnancy. Given that inadequate dosing for prevention or treatment of malaria in pregnancy can result in negative maternal/infant outcomes, along with the potential to select for parasite drug resistance, it is imperative that reliable pregnancy-specific dosing recommendations are established.

The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysis.

Background: Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax.

A Randomized Open-Label Evaluation of the Antimalarial Prophylactic Efficacy of Azithromycin-Piperaquine versus Sulfadoxine-Pyrimethamine in Pregnant Papua New Guinean Women.

Emerging malaria parasite sulfadoxine-pyrimethamine (SP) resistance has prompted assessment of alternatives for intermittent preventive treatment in pregnancy (IPTp). The objective was to evaluate the tolerability and prophylactic efficacy of azithromycin (AZ) plus piperaquine (PQ) in pregnant women in Papua New Guinea. The study was an open-label, randomized, parallel-group trial.

Pharmacotherapy for the prevention of malaria in pregnant women: currently available drugs and challenges.

Introduction: Malaria in pregnancy continues to be a significant public health burden globally, with over 100 million women at risk each year. Sulfadoxine-pyrimethamine (SP) is the only antimalarial recommended for intermittent preventive therapy in pregnancy (IPTp) but increasing parasite resistance threatens its viability. There are few other available antimalarial therapies that currently have sufficient evidence of tolerability, safety, and efficacy to replace SP.

Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration.

Mass drug administration (MDA) of sequential rounds of antimalarial drugs is being considered for use as a tool for malaria elimination. As an effective and long-acting antimalarial, dihydroartemisinin-piperaquine (DHA-PQP) appears to be suitable as a candidate for MDA. However, the absence of cardiac safety data following repeated administration hinders its use in the extended schedules proposed for MDA.

Validation of a Dried Blood Spot Ceftriaxone Assay in Papua New Guinean Children with Severe Bacterial Infections.

Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK) studies in situations where venous blood sampling is logistically and/or ethically challenging. In this study, we aimed to demonstrate the validity of a DBS ceftriaxone assay in a PK study of children with severe illness from Papua New Guinea (PNG), a setting in which health care resources are limited and anemia is common. Using a previously validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, serial plasma and DBS ceftriaxone concentrations were measured in PNG children aged 5 to 10 years with acute bacterial meningitis or severe pneumonia.

Artemisinin Therapy for Malaria in Hemoglobinopathies: A Systematic Review.

Artemisinin derivatives are widely used antimalarial drugs. There is some evidence from in vitro, animal and clinical studies that hemoglobinopathies may alter their disposition and antimalarial activity. This review assesses relevant data in α-thalassemia, sickle cell disease (SCD), β-thalassemia and hemoglobin E.

Cost-effectiveness of artemisinin-naphthoquine versus artemether-lumefantrine for the treatment of uncomplicated malaria in Papua New Guinean children.

Background: A recent randomized trial showed that artemisinin-naphthoquine (AN) was non-inferior to artemether-lumefantrine (AL) for falciparum malaria and superior for vivax malaria in young Papua New Guinean children. The aim of this study was to compare the cost-effectiveness of these two regimens.

Methods: An incremental cost-effectiveness analysis was performed using data from 231 children with Plasmodium falciparum and/or Plasmodium vivax infections in an open-label, randomized, parallel-group trial.