Association of Vancomycin AUC/MIC and Trough Concentration With Early Clinical Response in Enterococcus or Coagulase-Negative Staphylococcus Infection: A Prospective Study.

This study was condcuted to examine the association of area under the curve (AUC)/minimum inhibitory concentration (MIC) and trough concentration (C) of vancomycin with treatment outcome and nephrotoxicity in infections caused by Enterococcus spp. and coagulase-negative Staphylococci (CoNS). Peak and trough concentrations were used to calculate AUC in 89 patients receiving vancomycin for infections with Enterococcus spp.

The Development of a Physiologically Based Pharmacokinetic (PBPK) Model of Andrographolide in Mice and Scaling it up to Rats, Dogs, and Humans.

Background: Andrographolide has a potent antiviral effect in the treatment of coronavirus disease (COVID-19). However, there are no in vivo studies of andrographolide as an anti-COVID-19 treatment.

Objective: The study aims to develop a physiologically based pharmacokinetic (PBPK) animal model and scale it up to a human model to predict andrographolide concentrations in the lungs.

Development and Qualification of a Physiologically Based Pharmacokinetic Model of Finasteride and Minoxidil Following Scalp Application.

In this study, we aimed to develop and qualify a PBPK model for scalp application using two drugs with marked differences in physicochemical properties and PK profiles. The parameters related to scalp physiology, drug PK, and formulations were incorporated into a Multi-Phase and Multi-Layer (MPML) Mechanistic Dermal Absorption (MechDermA) model within the Simcyp® Simulator V17. The finasteride PBPK model was linked to its effect on dihydrotestosterone (DHT) levels in plasma and scalp using an indirect response model.

Population Pharmacokinetic Modeling of Vancomycin in Thai Patients With Heterogeneous and Unstable Renal Function.

Background: Vancomycin is widely used to treat gram-positive bacterial infections. However, given significant interpatient variability in its pharmacokinetics, maintaining plasma concentrations is difficult within its characteristically narrow therapeutic window. This is especially challenging in patients with unstable renal function.

Strategies to enhance oral delivery of amphotericin B: a comparison of uncoated and enteric-coated nanostructured lipid carriers.

The oral delivery of amphotericin B (AmB) has remained a challenge due to its low solubility, permeability, and instability in gastric acidic pH. To solve these issues, herein, we reported a novel approach of using nanostructured lipid carriers (NLCs) and NLCs coating with EudragitL100-55 (Eu-NLCs) for the oral delivery of AmB. This study aimed to compare their ability in protecting the drug from degradation in gastrointestinal fluids and permeation enhancement in Caco-2 cells.

Pomegranate Juice does not Affect the Bioavailability of Cyclosporine in Healthy Thai Volunteers.

Background: It is still controversial whether pomegranate causes drug interactions. Pomegranate juice has been shown to inhibit CYP3A in-vitro and animal studies. The coadministration of pomegranate juice with cyclosporine, a narrow therapeutic drug that is the substrate of CYP3A, might lead to drug toxicity.

Modeling the heterogeneous intestinal absorption of propiverine extended-release.

Propiverine is a widely used antimuscarinic drug with bioavailability that is limited by intestinal first-pass extraction. To study the apparent heterogeneity in intestinal first-pass extraction, we performed a population analysis of oral concentration-time data measured after administration of an extended-release formulation of propiverine in ten healthy subjects. Using an inverse Gaussian function as input model, the assumption that the systemically available fraction increases as a sigmoidal function of time considerably improved the fit.

Pomelo enhances cyclosporine bioavailability in healthy male Thai volunteers.

The aim of this study was to investigate the effect of pomelo pulp on the pharmacokinetics of cyclosporine in healthy male Thai volunteers. The study design was an open-label, randomized, single dose, crossover study with a 2-week washout period. A single oral dose of 2 × 100 mg cyclosporine was administered with 200 mL of water.

Modeling the kinetics of digoxin absorption: enhancement by P-glycoprotein inhibition.

An increase in the area under the curve (AUC) after oral digoxin due to coadministration of drugs known as P-glycoprotein (P-gp) inhibitors has been reported in several studies, but there is very little information on the rate of absorption after P-gp inhibition. Based on an inverse Gaussian density absorption model and using a population approach, the authors reanalyzed data showing an increase in oral digoxin AUC in healthy volunteers after coadministration of talinolol. The model fitted the data well, and the results revealed that the maximum rate of digoxin absorption increased nearly 2-fold, whereas bioavailability increased only by 21%.

Pharmacokinetic-pharmacodynamic modeling of the effect of propofol on alpha 1-adrenoceptor-mediated positive inotropy in rat heart.

Since it is unclear whether and how propofol affects the alpha(1)-mediated inotropic response, we used a pharmacokinetic-pharmacodynamic modeling approach in isolated rat hearts to analyze the effect of propofol on receptor binding and signal transduction. In Langendorff rat hearts perfused with buffer containing 12.3 microM phenylephrine, 1.

Reduced uptake of liposomal idarubicin in the perfused rat heart.

Although idarubicin is one of the most important anthracyclines and liposomal formulations seemed less cardiotoxic than free drug formulations, there are no definite data on cardiac uptake of liposomal encapsulated idarubicin. This study has been designed to determine uptake and negative inotropic action of liposomal idarubicin in the single-pass isolated perfused rat heart. Idarubicin-bearing liposomes, composed of 1,2-distearoyl-sn-glicero-phosphocholine, 1,2-distearoyl-sn-glicero-phosphoethanolamine-N-[poly(ethylene glycol)2000], and cholesterol were administered as a 10-min constant infusion of 1 mg followed by a 70-min washout period.

Cardiac pharmacokinetics and inotropic response of verapamil in rats with endotoxemia.

The present study evaluated the effect of endotoxin-induced systemic inflammation on cardiac uptake and negative inotropic response to verapamil in isolated rat hearts. Rats received an i.p.

Modeling cardiac uptake and negative inotropic response of verapamil in rat heart: effect of amiodarone.

Purpose: To determine the effect of the P-glycoprotein (Pgp) modulator amiodarone on the pharmacokinetics and pharmacodynamics (PK/PD) of Pgp substrate verapamil in the perfused rat heart.

Methods: In Langendorff-perfused rat hearts, the outflow concentration-time curve and inotropic response data were measured after a 1.5 nmol dose of [3H]-verapamil (infused within 1 min) in the absence and presence of the amiodarone (1 microM) in perfusate, as well as using a double dosing regimen (0.

Kinetic analysis of myocardial uptake and negative inotropic effect of amiodarone in rat heart.

The distribution kinetics of the highly lipophilic antiarrhythmic agent amiodarone is not well understood. The purpose of the present investigation was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model to describe cardiac uptake and the negative inotropic effect of amiodarone in the isolated perfused rat heart. Amiodarone (10 microM) was infused for 15 min to 6 hearts.