Pharmacokinetic and Pharmacodynamic Analyses To Determine the Optimal Fixed Dosing Regimen of Iclaprim for Treatment of Patients with Serious Infections Caused by Gram-Positive Pathogens.

Iclaprim is a bacterial dihydrofolate reductase inhibitor that is currently being evaluated in two phase 3 trials for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Prior animal infection model studies suggest that the pharmacokinetic/pharmacodynamic (PK/PD) drivers for efficacy are area under the concentration-time curve from 0 to 24 h at steady state (AUC), AUC/MIC, and time above the MIC during the dosing interval ( > MIC), while QTc prolongation was associated with the maximal concentration at steady state () in a thorough QTc phase 1 study. Using PK data collected from 470 patients from the previously conducted phase 3 complicated skin and skin structure infection (cSSSI) trials, population PK modeling and Monte Carlo simulation (MCS) were used to identify a fixed iclaprim dosage regimen for the ongoing phase 3 ABSSSI studies that maximizes AUC, AUC/MIC, and > MIC while minimizing the probability of a of ≥800 ng/ml relative to the values for the previously employed cSSSI regimen of 0.

Four-Factor Prothrombin Complex Concentrate for Coagulopathy Reversal in Patients With Liver Disease.

A 4-factor prothrombin complex concentrate (4F-PCC, Kcentra®) was recently approved in the United States for the reversal of vitamin K antagonist-associated major bleeding, but it is often used to reverse coagulopathy in patients with liver disease (LD). This single-center, retrospective study analyzed the efficacy and safety of 4F-PCC administered in patients with and without LD. Prothrombin time/International Normalized Ratio (PT/INR) reversal with 4F-PCC was attempted in 85 patients; LD was documented in 31 patients.

Plasma Levels of Advanced Glycation End Products Are Related to the Clinical Presentation and Angiographic Severity of Symptomatic Lower Extremity Peripheral Arterial Disease.

Evidence implicates a role of advanced glycation end products (AGEs) in the development of atherosclerosis. The present study examined the relationship between plasma levels of AGEs and the clinical and angiographic characteristics of patients with symptomatic peripheral arterial disease (PAD). A total of 40 consecutive patients with symptomatic lower extremity PAD undergoing invasive evaluation were enrolled.

High-fidelity simulation training in advanced resuscitation for pharmacy residents.

Objective: To assess the impact of high-fidelity patient simulation on pharmacy resident knowledge, confidence, and competency with advanced resuscitation algorithms and interventions.

Design: An overview of the institutional cardiopulmonary arrest algorithm and a review of pertinent medications and calculations were presented to postgraduate year 1 (PGY1) pharmacy residents, followed by participation in 3 simulated clinical scenarios using a high-fidelity mannequin.

Assessment: An improvement of pharmacy resident knowledge, confidence, and competency with advanced resuscitation skills was observed.

Plerixafor as first- and second-line strategies for autologous stem cell mobilization in patients with non-Hodgkin's lymphoma or multiple myeloma.

Study Objective: To describe the institutional experience of plerixafor plus filgrastim as the initial peripheral blood stem cell (PBSC) mobilization (first-line strategy) and as rescue therapy after failure with filgrastim plus cyclophosphamide (second-line strategy).

Design: Retrospective medical record review.

Setting: Academic medical center.

Inclusion of a CRF01_AE HIV envelope protein boost with a DNA/MVA prime-boost vaccine: Impact on humoral and cellular immunogenicity and viral load reduction after SHIV-E challenge.

The current study assessed the immunogenicity and protective efficacy of various prime-boost vaccine regimens in rhesus macaques using combinations of recombinant DNA (rDNA), recombinant MVA (rMVA), and subunit gp140 protein. The rDNA and rMVA vectors were constructed to express Env from HIV-1 subtype CRF01_AE and Gag-Pol from CRF01_AE or SIVmac 239. One of the rMVAs, MVA/CMDR, has been recently tested in humans.

Breast milk hydrocodone and hydromorphone levels in mothers using hydrocodone for postpartum pain.

Objective: To estimate the extent of passage of hydrocodone and its active metabolite, hydromorphone, into breast milk.

Methods: This is a pharmacokinetic study of 30 postpartum women receiving hydrocodone bitartrate for postpartum pain in the inpatient setting. Mothers donated timed breast milk samples for the analysis of hydrocodone and hydromorphone.

Hydrocodone excretion into breast milk: the first two reported cases.

Hydrocodone is a narcotic that is widely used, often in nursing mothers. Although case reports suggest that hydrocodone in breast milk sometimes may be problematic for the breastfed infant, no reports exist on the amount of its excretion into breast milk. Two mothers who were taking an acetaminophen and hydrocodone combination product donated pumped milk for analysis of hydrocodone.

Inhibition of pentagastrin-stimulated gastric acid secretion by pantoprazole and omeprazole in healthy adults.

Our objective was to compare the onset and duration of a single dose of pantoprazole or omeprazole on maximally stimulated gastric acid secretion. This double-blind, randomized, placebo-controlled study involved 36 healthy adults and utilized continuous pentagastrin infusion to stimulate acid secretion after administration of pantoprazole, 40 mg, omeprazole, 20 mg, or placebo. Gastric aspirates were collected over 24 hr and analyzed for volume, pH, and hydrogen ion concentration, and gastric acid outputs (GAO) were calculated.

Pharmacokinetics of UH and LMWH are similar with respect to antithrombin activity.

Background: The ability to administer low molecular weight heparins (LMWH) subcutaneously without laboratory monitoring contributes to their popularity for the treatment of thrombotic disorders. Subcutaneous unfractionated heparin, although less expensive, is deemed to require routine laboratory monitoring on the basis of more variability in drug effect compared to LMWH. However, the more predictable pharmacokinetic profiles of low molecular weight heparins are largely based on anti-Xa activity, while antithrombin activity may be at least as important to their mechanisms of action.

Population pharmacokinetics III: design, analysis, and application of population pharmacokinetic Studies.

Objective: To present a framework within which population pharmacokinetic (PPK) studies should be designed and analyzed and discuss the application of developed PPK models.

Methods: Information on PPK was retrieved from a MEDLINE search (1979-December 2003) of the literature and a bibliographic evaluation of review articles and books. This information is used in conjunction with experience to explain the design and analysis of PPK studies.

Model appropriateness and population pharmacokinetic modeling.

The purpose of this study was to define model appropriateness, identifying the individual elements thereof, and to set out a framework within which model appropriateness could be determined for population pharmacokinetic (PPK) models. Model appropriateness was defined by stating the problem to be solved, with the intended use of the model being the pivotal event. The elements of model appropriateness were identified with the type of model (descriptive vs.

Among 46 near full length HIV type 1 genome sequences from Rakai District, Uganda, subtype D and AD recombinants predominate.

The impact of HIV-1 genetic diversity on candidate vaccines is uncertain. To minimize genetic diversity in the evaluation of HIV-1 vaccines, vaccine products must be matched to the predominant subtype in a vaccine cohort. To that end, full genome sequencing was used to detect and characterize HIV-1 subtypes and recombinant strains from individuals in Rakai District, Uganda.