A Physiologically-Based Pharmacokinetic Simulation to Evaluate Approaches to Mitigate Efavirenz-Induced Decrease in Levonorgestrel Exposure with a Contraceptive Implant.

Levonorgestrel implant is a highly effective hormonal contraceptive, but its efficacy may be compromised when used with cytochrome enzyme inducers such as efavirenz. The primary aim of this study was to evaluate methods of mitigating the drug interaction. Using a physiologically-based pharmacokinetic (PBPK) model for levonorgestrel that we developed within the Simcyp program, we evaluated a higher dose of levonorgestrel implant, a lower dose of efavirenz, and the combination of both, as possible methods to mitigate the interaction.

Population Pharmacokinetic Properties of Piperaquine in Falciparum Malaria: An Individual Participant Data Meta-Analysis.

Background: Artemisinin-based combination therapies (ACTs) are the mainstay of the current treatment of uncomplicated Plasmodium falciparum malaria, but ACT resistance is spreading across Southeast Asia. Dihydroartemisinin-piperaquine is one of the five ACTs currently recommended by the World Health Organization. Previous studies suggest that young children (<5 y) with malaria are under-dosed.

Population Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria.

Background: The pharmacokinetics and pharmacodynamics of lumefantrine, a component of the most widely used treatment for malaria, artemether-lumefantrine, has not been adequately characterized in young children.

Methods: Capillary whole-blood lumefantrine concentration and treatment outcomes were determined in 105 Ugandan children, ages 6 months to 2 years, who were treated for 249 episodes of Plasmodium falciparum malaria with artemether-lumefantrine.

Results: Population pharmacokinetics for lumefantrine used a 2-compartment open model with first-order absorption.

Rethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study.

Background: The combination of short-acting dihydroartemisinin and long-acting piperaquine (DP) is among the first-line therapies for the treatment of uncomplicated Plasmodium falciparum malaria. Population pharmacokinetic models of piperaquine (PQ) based on data from acute treatment of young children can be used to predict exposure profiles of piperaquine under different DP chemoprevention regimens. The purpose of our study was to make such predictions in young children.

Enoxaparin thromboprophylaxis in gastric bypass patients: extended duration, dose stratification, and antifactor Xa activity.

Background: Morbidly obese patients undergoing gastric bypass surgery are at risk for postoperative venous thromboembolism. Evidence-based recommendations regarding the dosing and duration of thromboprophylaxis are lacking for morbidly obese surgical patients. The aims of this study were to evaluate the safety and efficacy of an extended duration, body mass index (BMI)-stratified enoxaparin thromboprophylaxis regimen in patients undergoing Roux-en-Y gastric bypass and to determine the resultant antifactor Xa (AFXa) activity in morbidly obese surgical patients.

Pharmacokinetics of single-dose levonorgestrel in adolescents.

Purpose: The purpose of this study is to compare the pharmacokinetics of levonorgestrel, a drug used for emergency contraception between female adolescents and adults.

Methods: Twenty-two female subjects, aged 13-16 years, received a single 0.75-mg dose of the drug.