Pharmacokinetics of oral spironolactone in infants up to 2 years of age.

Purpose: Spironolactone is a potassium sparing diuretic used for decades. Until now, pharmacokinetic (PK) studies of spironolactone have not been conducted in infants and therefore pediatric dosing is based on expert opinion. We aimed to describe the PK profiles of spironolactone and its main metabolites (7alpha-thiomethylspironolactone (TMS) and canrenone (CAN)) in infants up to two years of age.

Population pharmacokinetics and pharmacodynamics of dobutamine in neonates on the first days of life.

Aims: To describe the pharmacokinetics (PK) and concentration-related effects of dobutamine in critically ill neonates in the first days of life, using nonlinear mixed effects modelling.

Methods: Dosing, plasma concentration and haemodynamic monitoring data from a dose-escalation study were analysed with a simultaneous population PK and pharmacodynamic model. Neonates receiving continuous infusion of dobutamine 5-20 μg kg min were included.

A sensitive method for the simultaneous UHPLC-MS/MS analysis of milrinone and dobutamine in blood plasma using NHF as the eluent additive and ascorbic acid as a stabilizer.

The purpose of this work was to develop and validate an HPLC-MS/MS method suitable for quantifying two important cardiovascular drugs, milrinone and dobutamine, in neonatal and paediatric patients' blood plasma samples. Sufficiently low LLOQ levels were required to obtain adequate pharmacokinetic data for the evaluation of optimal dosing. Since the specifics of the patient group set some restrictions on the available sample volume, the method was designed to use only 20 µL of plasma for the analysis.

Population Pharmacokinetics and Dosing of Milrinone After Patent Ductus Arteriosus Ligation in Preterm Infants.

Objectives: The postoperative course of patent ductus arteriosus ligation is often complicated by postligation cardiac syndrome, occurring in 10-45% of operated infants. Milrinone might prevent profound hemodynamic instability and improve the recovery of cardiac function in this setting. The present study aimed to describe the population pharmacokinetics of milrinone in premature neonates at risk of postligation cardiac syndrome and give dosing recommendations.

Utilization of data below the analytical limit of quantitation in pharmacokinetic analysis and modeling: promoting interdisciplinary debate.

Traditionally, bioanalytical laboratories do not report actual concentrations for samples with results below the LOQ (BLQ) in pharmacokinetic studies. BLQ values are outside the method calibration range established during validation and no data are available to support the reliability of these values. However, ignoring BLQ data can contribute to bias and imprecision in model-based pharmacokinetic analyses.

Sponge Spray-Reaching New Dimensions of Direct Sampling and Analysis by MS.

Sample preparation for the analysis of clinical samples with the mass spectrometer (MS) can be extensive and expensive. Simplifying and speeding up the process would be very beneficial. This paper reports sponge spray-a novel sampling and direct MS analysis approach-attempting exactly that.

Signal Enhancement in the HPLC-ESI-MS/MS analysis of spironolactone and its metabolites using HFIP and NHF as eluent additives.

This paper describes an LC-MS/MS method to determine the concentration of spironolactone and its metabolites 7-alpha-methylthiospironolactone and canrenone in blood plasma samples. The resulting assay is simple (using protein precipitation for sample preparation) and sensitive (the lower limit of quantification is close to 0.5 ng/ml) while requiring only 50 μl of plasma, making it especially suitable for analyzing samples obtained from pediatric and neonatal patients where sample sizes are limited.

Virtual Screening for HIV Protease Inhibitors Using a Novel Database Filtering Procedure.

A virtual screening to find novel inhibitors for HIV protease was performed on the ZINC database.1 A critical part in virtual screening and associated techniques is preliminary database filtering and size reduction and for that purpose a novel feature matrix matching procedure was used. The reduction of ∼14 million available ligands to a subset of 14299 ligands was achieved with a structure based approach where the analysis of the 3D structure of the active site of the protease produced a graph with hydrogen bond donor, hydrogen bond acceptor and hydrophobic subsites represented as graph nodes.

Combined approach using ligand efficiency, cross-docking, and antitarget hits for wild-type and drug-resistant Y181C HIV-1 reverse transcriptase.

New hits against HIV-1 wild-type and Y181C drug-resistant reverse transcriptases were predicted taking into account the possibility of some of the known metabolism interactions. In silico hits against a set of antitargets (i.e.