Pharmacokinetic and pharmacokinetic/pharmacodynamic characterization of the dolutegravir/rilpivirine two-drug regimen in SWORD-1/-2 phase 3 studies.

Aim: SWORD-1 and SWORD-2 phase 3 studies concluded that switching virologically suppressed participants with HIV-1 from their current three- or four-drug antiretroviral regimen (CAR) to the two-drug regimen of once-daily dolutegravir (DTG, 50 mg) and rilpivirine (RPV, 25 mg) was safe, well tolerated and noninferior for maintaining HIV-1 suppression at week 48 and highly efficacious to week 148. A secondary objective was to characterize drug exposure and exposure-efficacy/safety relationships.

Methods: Adults with plasma HIV-1 RNA <50 copies/mL were randomized to switch to once-daily DTG + RPV on day 1 or to continue CAR for 52 weeks before switching.

Current strategies to streamline pharmacotherapy for older adults.

Although the term "personalized medicine" has been associated in many cases with pharmacogenomics, its definition embraces the use of specific biomarkers and covariates to help in the selection of medical treatments and procedures which are best for each patient. While several efforts have been performed for the tailored selection of therapies and dosing regimens in the general population, developing personalized medicine initiatives for elderly patients remains understudied. The personalized drug therapy for older patients requires the consideration of anatomical, physiological and functional alterations in a multimorbid setting requiring multiple medications.

How Informative Are Drug-Drug Interactions of Gene-Drug Interactions?

FDA recommendations to manage polymorphic CYP-mediated drug-drug interactions (DDIs) and gene-drug interactions (GDIs) are typically similar. However, DDIs may not always reliably predict GDIs because the victim drug may have multiple metabolic pathways and the perpetrator drug may affect multiple enzymes or transporters. Consequently, it is of great interest to both the pharmaceutical industry and regulatory agencies to determine if DDI studies can be leveraged to inform GDIs or vice versa for dose adjustment and labeling.

Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration.

Levofloxacin (LEV) is a broad-spectrum fluoroquinolone used to treat pneumonia, urinary tract infections, chronic bacterial bronchitis, and prostatitis. Efflux transporters, primarily P-glycoprotein (P-gp), are involved in LEV's tissue penetration. In the present work, LEV free lung and prostate interstitial space fluid (ISF) concentrations were evaluated by microdialysis in Wistar rats after intravenous (i.

Evaluation of Approaches to Deal with Low-Frequency Nuisance Covariates in Population Pharmacokinetic Analyses.

Clinical studies include occurrences of rare variables, like genotypes, which due to their frequency and strength render their effects difficult to estimate from a dataset. Variables that influence the estimated value of a model-based parameter are termed covariates. It is often difficult to determine if such an effect is significant, since type I error can be inflated when the covariate is rare.

A reduction in between subject variability is not mandatory for selecting a new covariate.

Population pharmacokinetic-pharmacodynamic analysis involves nonlinear hierarchical modelling where the mean response in a population and the variability in response from different sources are studied. It generally consists of two model hierarchies: a model for residual error and a model for heterogeneity termed between subject variance (BSV). The overall variability in a parameter within a population termed population parameter variance (PPV) consists of within subject variance (WSV) and BSV.

Design of pharmacokinetic studies for latent covariates.

Latent covariates are covariates that are known to exist but are either observable but unavailable or unobservable at the time of the clinical study. Designs to account for latent covariates must incorporate both uncertainty in the prevalence of the covariate and the data-type of the covariate. The informativeness of the covariate will then depend on whether the covariate data is continuous, ordinal or nominal.

Polyamines: Potential anti-inflammatory agents and their possible mechanism of action.

Objective: To evaluate the anti-inflammatory activity of exogenously administered polyamines on experimentally induced acute and chronic inflammation in wistar rats and to elucidate their possible mechanism of action.

Materials And Methods: The in vivo anti-inflammatory activity of polyamines was studied using acute (carrageenin paw edema), sub-acute (cotton pellet granuloma) and chronic (Freund's adjuvant induced arthritis) models of inflammation. The biochemical parameters like liver lipid peroxides, SGOT and SGPT were also measured.

An experimental evaluation of the antidiabetic and antilipidemic properties of a standardized Momordica charantia fruit extract.

Background: The MCE, Momordica charantia fruit extract Linn. (Cucurbitaceae) have been documented to elicit hypoglycemic activity on various occasions. However, due to lack of standardization of these extracts, their efficacy remains questionable.