Monte Carlo simulation evaluation of tigecycline dosing for bacteria with raised minimum inhibitory concentrations in non-critically ill adults.

Purpose: Tigecycline is one of few antibiotics active against multidrug-resistant bacteria; however, the assessment of dosing strategies to optimize its activity is needed. The purpose was to use Monte Carlo Simulation (MCS) to determine if safe tigecycline dosing options attaining breakpoints for pharmacokinetic/pharmacodynamic (PK-PD) targets in non-critically ill adults could be identified.

Methods: Publications that evaluated tigecycline dosing regimens and provided mean PK variables of interest (minimum 2 of: elimination rate constant or half-life and volume of distribution or clearance), with SDs, were included.

N Solid-State NMR Spectroscopy of Amino Acids.

N ultra-wideline solid-state NMR (SSNMR) spectra were obtained for 16 naturally occurring amino acids and four related derivatives by using the WURST-CPMG (wideband, uniform rate, and smooth truncation Carr-Purcell-Meiboom-Gill) pulse sequence and frequency-stepped techniques. The N quadrupolar parameters were measured for the sp nitrogen moieties (quadrupolar coupling constant, C , values ranged from 0.8 to 1.

Natural abundance (14)N and (15)N solid-state NMR of pharmaceuticals and their polymorphs.

(14)N ultra-wideline (UW), (1)H{(15)N} indirectly-detected HETCOR (idHETCOR) and (15)N dynamic nuclear polarization (DNP) solid-state NMR (SSNMR) experiments, in combination with plane-wave density functional theory (DFT) calculations of (14)N EFG tensors, were utilized to characterize a series of nitrogen-containing active pharmaceutical ingredients (APIs), including HCl salts of scopolamine, alprenolol, isoprenaline, acebutolol, dibucaine, nicardipine, and ranitidine. A case study applying these methods for the differentiation of polymorphs of bupivacaine HCl is also presented. All experiments were conducted upon samples with naturally-abundant nitrogen isotopes.