pharmacokinetics
Experimental TherapeuticsFormulation, Pharmacological Evaluation, and Efficacy Studies of Occidiofungin, a Novel AntifungalOccidiofungin is a nonribosomally synthesized cyclic lipopeptide that possesses broad-spectrum antifungal properties at submicromolar concentrations. This report explores multiple routes of administration and formulations of occidiofungin, as well as its toxicity in mice. Further, infection studies were performed in mice to assess the application of occidiofungin for treating systemic and intravaginal yeast infections. Formulations for...
PharmacologyImpact of Intraoperative Cell Salvage on Concentrations of Antibiotics Used for Surgical ProphylaxisIntraoperative cell salvage (IOCS) is used to administer autologous blood lost during surgery. We studied antibiotic disposition through an ex vivo IOCS system for vancomycin, piperacillin, ampicillin, and cefazolin. Only 2% ± 1% of antibiotic inoculated in whole blood was recovered in the IOCS reinfusion bag, whereas 97% ± 17% was found in the waste. These observations were confirmed for ampicillin in two patients undergoing...
PharmacologyImpact of Loading Dose of Caspofungin in Pharmacokinetic-Pharmacodynamic Target Attainment for Severe Candidiasis Infections in Patients in Intensive Care Units: the CASPOLOAD StudyThis study evaluated the impact of a high loading dose of caspofungin (CAS) on the pharmacokinetics of CAS and the pharmacokinetic-pharmacodynamic (PK-PD) target attainment in patients in intensive care units (ICU). ICU patients requiring CAS treatment were prospectively included to receive a 140-mg loading dose of CAS. Plasma CAS concentrations (0, 2, 3, 5, 7, and 24 h postinfusion) were determined to develop a two-compartmental...
Clinical TherapeuticsPiperaquine Exposure Is Altered by Pregnancy, HIV, and Nutritional Status in Ugandan WomenDihydroartemisinin-piperaquine (DHA-PQ) provides highly effective therapy and chemoprevention for malaria in pregnant African women. PQ concentrations of >10.3 ng/ml have been associated with reduced maternal parasitemia, placental malaria, and improved birth outcomes. We characterized the population pharmacokinetics (PK) of PQ in a post hoc analysis of human immunodeficiency virus (HIV)-infected and -uninfected pregnant...
PharmacologyCharacteristics of Dolutegravir and Bictegravir Plasma Protein Binding: a First Approach for the Study of Pharmacologic SanctuariesThis study aimed to characterize in vitro dolutegravir (DTG) and bictegravir (BIC) binding. They had a preferential binding to human serum albumin (HSA) with two classes of albumin sites. Human alpha-1-acid glycoprotein (HAAG) binding of DTG and BIC showed an atypical nonlinear binding. The low-affinity site on HSA, the main plasma binding protein, suggests that the high protein binding rate should not impair passive diffusion...
Antiviral AgentsA Five-in-One First-in-Human Study To Assess Safety, Tolerability, and Pharmacokinetics of RO7049389, an Inhibitor of Hepatitis B Virus Capsid Assembly, after Single and Multiple Ascending Doses in Healthy ParticipantsRO7049389, an inhibitor of hepatitis B virus (HBV) capsid assembly, is being developed for the treatment of patients with chronic HBV infection. The objectives of this first-in-human study are to assess the safety, tolerability, pharmacokinetics (PK), food effect, inhibitory effect on CYP3A, and effect on QT of RO7049389 in healthy participants. Five components, single-ascending-dose (SAD) cohorts, multiple-ascending-dose (MAD) cohorts...
Experimental TherapeuticsAssessing the Safety, Tolerability, Pharmacokinetics, and Biodistribution of Novel Oral Formulations of Amphotericin B following Single- and Multiple-Dose Administration to Beagle DogsThe purpose of this study was to assess the safety, tolerability, pharmacokinetics (PK), and biodistribution of novel oral amphotericin B (AmpB) formulations following single- and multiple-oral-dose administration to healthy beagle dogs. The liquid formulation of AmpB was administered to three male dogs, and the capsule formulations of AmpB were administered to each of two groups of six male dogs. Blood was collected for pharmacokinetic...
Antiviral AgentsRemoval of Remdesivir’s Metabolite GS-441524 by Hemodialysis in a Double Lung Transplant Recipient with COVID-19Remdesivir has reported efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and in vivo. Drug-drug interactions limit therapeutic options in transplant patients. Remdesivir and its metabolite GS-441524 are excreted principally in urine. In intensive care unit (ICU) settings, in which multiple-organ dysfunctions can occur rapidly, hemodialysis may be a viable option for maintaining...
PharmacologyAn Open-Label Study of the Impact of Hepatic Impairment on the Pharmacokinetics and Safety of Single Oral and Intravenous Doses of OmadacyclineOmadacycline is a once-daily oral or intravenous (i.v.) aminomethylcycline antibiotic approved in the United States for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults. Omadacycline pharmacokinetics were characterized in 18 patients with hepatic impairment and 12 matched healthy subjects. Patients with hepatic impairment received i.v. omadacycline...
PharmacologyPopulation Pharmacokinetics of Caspofungin among Extracorporeal Membrane Oxygenation Patients during the Postoperative Period of Lung TransplantationLittle is known about the influence of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of caspofungin. The aim of this study was to describe population PK of caspofungin in patients with and without ECMO during the postoperative period of lung transplantation (LTx) and to investigate covariates influencing caspofungin PK. We compared ECMO patients with non-ECMO patients, and patients before and after ECMO weaning...