pharmacokinetics
PharmacologyPopulation Pharmacokinetic Study of the Suitability of Standard Dosing Regimens of Amikacin in Critically Ill Patients with Open-Abdomen and Negative-Pressure Wound TherapyThe aim was to assess the appropriateness of recommended regimens for empirical MIC coverage in critically ill patients with open-abdomen and negative-pressure therapy (OA/NPT). Over a 5-year period, every critically ill patient who received amikacin and who underwent therapeutic drug monitoring (TDM) while being treated by OA/NPT was retrospectively included. A population pharmacokinetic (PK) modeling was performed considering the...
Clinical TherapeuticsSafety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy VolunteersMMV390048 is a novel antimalarial compound that inhibits Plasmodium phosphatidylinositol-4-kinase. The safety, tolerability, pharmacokinetic profile, and antimalarial activity of MMV390048 were determined in healthy volunteers in three separate studies. A first-in-human, double-blind, randomized, placebo-controlled, single-ascending-dose study was performed....
Clinical TherapeuticsHigh-Dose Chloroquine for Uncomplicated Plasmodium falciparum Malaria Is Well Tolerated and Causes Similar QT Interval Prolongation as Standard-Dose Chloroquine in ChildrenHigher chloroquine doses can effectively treat up to 93 to 96% of malaria infections caused by Plasmodium falciparum carrying the resistance-conferring chloroquine resistance transporter (pfcrt) 76T allele. The tolerability of 50 (double the standard dose) and 70 mg/kg total chloroquine doses were assessed in this study. Fifteen 4- to 8-year-old children with...
PharmacologyA Population Pharmacokinetics and Pharmacodynamic Approach To Optimize Tazobactam Activity in Critically Ill PatientsThe percentage of the time that the free drug concentration remains above a concentration threshold (%fT > concentration threshold) has frequently been identified to be the optimal pharmacokinetic (PK)-pharmacodynamic (PD) target of interest for tazobactam using in vitro infection models.
PharmacologyPharmacokinetics and Ex Vivo Antimalarial Activity of Artesunate-Amodiaquine plus Methylene Blue in Healthy VolunteersHigh rates of artemisinin-based combination therapy (ACT) failures in the treatment of Plasmodium falciparum malaria in Southeast Asia have led to triple-drug strategies to extend the useful life of ACTs. In this study, we determined whether methylene blue [MB; 3,7-bis(dimethylamino)phenothiazin-5-ium chloride hydrate] alters the pharmacokinetics of artesunate-...
PharmacologyDifferential Impact of Nevirapine on Artemether-Lumefantrine Pharmacokinetics in Individuals Stratified by CYP2B6 c.516G>T GenotypesThere is an increased recognition of the need to identify and quantify the impact of genetic polymorphisms on drug-drug interactions. This study investigated the pharmacogenetics of the pharmacokinetic drug-drug interaction between nevirapine and artemether-lumefantrine in HIV-positive and HIV-negative adult Nigerian subjects.
SusceptibilityIn Vivo Efficacy and Pharmacokinetics of the 2-Aminomethylphenol Antimalarial JPC-3210 in the Aotus Monkey-Human Malaria ModelNonimmune Aotus monkeys infected with Plasmodium falciparum and Plasmodium vivax were cured of their infections when treated with a single oral dose of 5 mg/kg and 10 mg/kg of the 2-aminomethylphenol, JPC-3210, respectively. Corresponding mean blood elimination half-lives of JPC-3210 were...
PharmacologyMeropenem-Tobramycin Combination Regimens Combat Carbapenem-Resistant Pseudomonas aeruginosa in the Hollow-Fiber Infection Model Simulating Augmented Renal Clearance in Critically Ill PatientsAugmented renal clearance (ARC) is common in critically ill patients and is associated with subtherapeutic concentrations of renally eliminated antibiotics. We investigated the impact of ARC on bacterial killing and resistance amplification for meropenem and tobramycin regimens in monotherapy and combination. Two carbapenem-resistant Pseudomonas aeruginosa isolates...
Clinical TherapeuticsTarget-Controlled Infusion of Cefepime in Critically Ill PatientsAttainment of appropriate pharmacokinetic-pharmacodynamic (PK-PD) targets for antimicrobial treatment is challenging in critically ill patients, particularly for cefepime, which exhibits a relative narrow therapeutic-toxic window compared to other beta-lactam antibiotics. Target-controlled infusion (TCI) systems, which deliver drugs to achieve specific target drug concentrations, have successfully been implemented for improved dosing of...
PharmacologyPharmacokinetics of Telavancin in Adult Patients with Cystic Fibrosis during Acute Pulmonary ExacerbationAdults with cystic fibrosis (CF) frequently harbor Staphylococcus aureus, which is increasingly antibiotic resistant. Telavancin is a once-daily rapidly bactericidal antibiotic active against methicillin-, linezolid-, and ceftaroline-resistant S. aureus. Because CF patients experience alterations in...