Population Pharmacokinetics of Olanzapine and Samidorphan When Administered in Combination in Healthy Subjects and Patients With Schizophrenia.

A combination of olanzapine and samidorphan was recently approved by the US Food and Drug Administration for the treatment of patients with schizophrenia or bipolar I disorder. Population pharmacokinetic models for olanzapine and samidorphan were developed using data from 11 clinical studies in healthy subjects or patients with schizophrenia. A 2-compartment disposition model with first-order absorption and elimination and a lag time for absorption adequately described concentration-time profiles of both olanzapine and samidorphan.

Population Pharmacokinetic Analysis and Model-Based Simulations of Aripiprazole for a 1-Day Initiation Regimen for the Long-Acting Antipsychotic Aripiprazole Lauroxil.

Unlabelled: BACKGROUND AND OBJECTIVES: Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic for the treatment of schizophrenia, requires 21 days of oral aripiprazole supplementation upon initiation (21-day initiation regimen). An alternative 1-day initiation regimen utilizing a nano-crystalline milled dispersion of AL (AL) plus a single 30 mg oral aripiprazole dose achieved aripiprazole concentrations associated with therapeutic doses of aripiprazole in the same time frame as the 21-day initiation regimen when starting AL (441 or 882 mg). A population pharmacokinetic (PopPK) model was developed to describe aripiprazole pharmacokinetics following administration of AL, AL and oral aripiprazole, and evaluate dosing scenarios likely to be encountered in clinical practice.

Oliceridine (TRV130), a Novel G Protein-Biased Ligand at the μ-Opioid Receptor, Demonstrates a Predictable Relationship Between Plasma Concentrations and Pain Relief. I: Development of a Pharmacokinetic/Pharmacodynamic Model.

Conventional opioids bind to μ-opioid receptors and activate 2 downstream signaling pathways: G-protein coupling, linked to analgesia, and β-arrestin recruitment, linked to opioid-related adverse effects and limiting efficacy. Oliceridine (TRV130) is a novel G protein-biased ligand at the μ-opioid receptor that differentially activates G-protein coupling while mitigating β-arrestin recruitment. Using data derived from both phase 1 studies in healthy volunteers as well as data from a phase 2 study examining the efficacy of oliceridine for the treatment of postbunionectomy pain, we have developed a population pharmacokinetic/pharmacodynamic model linking the pharmacokinetics of oliceridine to its effect on pain, as measured by the Numeric Pain Rating Scale score.

Oliceridine, a Novel G Protein-Biased Ligand at the μ-Opioid Receptor, Demonstrates a Predictable Relationship Between Plasma Concentrations and Pain Relief. II: Simulation of Potential Phase 3 Study Designs Using a Pharmacokinetic/Pharmacodynamic Model.

Oliceridine is a novel G protein-biased ligand at the μ-opioid receptor that differentially activates G protein coupling while mitigating β-arrestin recruitment. Unlike morphine, oliceridine has no known active metabolites; therefore, analgesic efficacy is predictably linked to its concentration in the plasma. Oliceridine is primarily hepatically metabolized by CYP3A4 and CYP2D6.

Crowdsourced Asparagus Urinary Odor Population Kinetics.

The consumption of asparagus is associated with the production of malodorous urine with considerable interindividual variability (IIV). To characterize the urinary odor kinetics after consumption of asparagus spears, we conducted a study with consenting attendees from two American Society for Clinical Pharmacology and Therapeutics (ASCPT) meetings. Subjects were randomized to eat a specific number of asparagus spears, and then asked to report their urinary odor perception.

Pharmacokinetic Profile of a 2-Month Dose Regimen of Aripiprazole Lauroxil: A Phase I Study and a Population Pharmacokinetic Model.

Background: Aripiprazole lauroxil (AL) is a long-acting injectable medication approved for the treatment of schizophrenia. Current AL regimens are 441 mg, 662 mg, and 882 mg administered monthly (every 4 weeks [q4wk]), or 882 mg administered every 6 weeks (q6wk).

Objective: We examined the feasibility of a 2-month (every 8 weeks [q8wk]) dosing interval of AL in a phase I open-label pharmacokinetic study investigating AL 1064 mg administered q8wk for 24 weeks, followed by 20 weeks of safety and pharmacokinetic measurements (ClinicalTrials.

Aripiprazole Lauroxil: Pharmacokinetic Profile of This Long-Acting Injectable Antipsychotic in Persons With Schizophrenia.

Background: Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice.

Methods: Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model.

Omnidirectional beacon-localization using a catadioptric system.

We present a catadioptric beacon localization system that can provide mobile network nodes with omnidirectional situational awareness of neighboring nodes. In this system, a receiver composed of a hyperboloidal mirror and camera is used to estimate the azimuth, elevation, and range of an LED beacon. We provide a general framework for understanding the propagation of error in the angle-of-arrival estimation and then present an experimental realization of such a system.

Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529.

BMS-663068 is an oral prodrug of the HIV-1 attachment inhibitor BMS-626529, which prevents viral attachment to host CD4(+) T cells by binding to HIV-1 gp120. To guide dose selection for the phase 3 program, pharmacokinetic/pharmacodynamic modeling was performed using data from two phase 2 studies with HIV-1-infected subjects (n = 244). BMS-626529 population pharmacokinetics were described by a two-compartment model with first-order elimination from the central compartment, zero-order release of prodrug from the extended-release formulation into a hypothetical absorption compartment, and first-order absorption into the central compartment.

Compressive spectral polarization imaging by a pixelized polarizer and colored patterned detector.

A compressive spectral and polarization imager based on a pixelized polarizer and colored patterned detector is presented. The proposed imager captures several dispersed compressive projections with spectral and polarization coding. Stokes parameter images at several wavelengths are reconstructed directly from 2D projections.

Dead time effects in non-line-of-sight ultraviolet communications.

By exploiting unique properties of the atmospheric propagation of radiation in the deep-ultraviolet band (200-300 nm), ultraviolet communications (UVC) offers the novel possibility of establishing non-line-of-sight (NLOS) optical links. UVC systems often employ photon-counting receivers, which may exhibit nonideal behavior owing to dead time, a period of time after the detection of a photon during which such a receiver is unable to detect subsequently impinging photons. In this paper, we extend a NLOS UVC channel model to account for dead time and then use this extended model to study the effects of dead time in representative system scenarios.

Population pharmacokinetics of dolutegravir in HIV-infected treatment-naive patients.

Aim: Dolutegravir is the newest integrase inhibitor approved for HIV treatment and has demonstrated potent antiviral activity in patient populations with a broad range of treatment experience. This analysis aimed to characterize the population pharmacokinetics of dolutegravir in treatment-naive patients and to evaluate the influence of patient covariates.

Methods: A population pharmacokinetic model was developed using a non-linear mixed effect modelling approach based on data from 563 HIV-infected, treatment-naive adult patients in three phase 2/3 trials who received dolutegravir (ranging from 10-50 mg once daily) alone or in combination with abacavir/lamivudine or tenofovir/emtricitabine.

Asynchronous compressed beamformer for portable diagnostic ultrasound systems.

State-of-the-art portable ultrasound imaging systems employ a small transducer array and a low carrier frequency to fit stringent constraints on power and form factor, and this tends to compromise the ultrasound imaging quality. In this paper, we present a low-complexity low-power asynchronous compressed beamformer (ACB) for portable diagnostic ultrasound. The proposed ACB integrates asynchronous sampling and compressive sensing (CS), and is capable of reducing data conversion power and handling a large data volume at the mixed-signal interface.

Biased agonism of the μ-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: A randomized, double-blind, placebo-controlled, crossover study in healthy volunteers.

Opioids provide powerful analgesia but also efficacy-limiting adverse effects, including severe nausea, vomiting, and respiratory depression, by activating μ-opioid receptors. Preclinical models suggest that differential activation of signaling pathways downstream of these receptors dissociates analgesia from adverse effects; however, this has not yet translated to a treatment with an improved therapeutic index. Thirty healthy men received single intravenous injections of the biased ligand TRV130 (1.

Design of dual-link (wide- and narrow-beam) LED communication systems.

We explore the design of an LED-based communication system comprising two free space optical links: one narrow-beam (primary) link for bulk data transmission and one wide-beam (beacon) link for alignment and support of the narrow-beam link. Such a system combines the high throughput of a highly directional link with the robust insensitivity to pointing errors of a wider-beam link. We develop a modeling framework for this dual-link configuration and then use this framework to explore system tradeoffs in power, range, and achievable rates.

Towards a Standard Mixed-Signal Parallel Processing Architecture for Miniature and Microrobotics.

The conventional analog-to-digital conversion (ADC) and digital signal processing (DSP) architecture has led to major advances in miniature and micro-systems technology over the past several decades. The outlook for these systems is significantly enhanced by advances in sensing, signal processing, communications and control, and the combination of these technologies enables autonomous robotics on the miniature to micro scales. In this article we look at trends in the combination of analog and digital (mixed-signal) processing, and consider a generalized sampling architecture.

Ultraviolet scattering propagation modeling: analysis of path loss versus range.

Modeling of the complex atmospheric propagation of deep-ultraviolet (UV) radiation is important for applications such as non-line-of-sight (NLOS) UV communications. Building upon prior work in which it was observed that short-range, singly scattered NLOS path loss varies linearly with range, we formalize this relationship, generalizing it to consider any order of scattering and more-general system characteristics. In particular, we derive the approximate relationship PL[proportionality]r(2-n) between path loss PL and range r for nth-order scattered radiation, and investigate the region of validity of this approximation.

An approximate closed-form link loss model for non-line-of-sight ultraviolet communication in noncoplanar geometry.

Non-line-of-sight UV communication link path loss models have been explored for both coplanar and noncoplanar geometries, and these typically require numerical evaluation. In this Letter, we propose a closed-form and easily applied model to describe link behavior, applicable to noncoplanar geometry. The model is compared with a recently reported analytical model and shows good agreement.

UV communications channel modeling incorporating multiple scattering interactions.

In large part because of advancements in the design and fabrication of UV LEDs, photodetectors, and filters, significant research interest has recently been focused on non-line-of-sight UV communication systems. This research in, for example, system design and performance prediction, can be greatly aided by accurate channel models that allow for the reproducibility of results, thus facilitating the fair and consistent comparison of different communication approaches. In this paper, we provide a comprehensive derivation of a multiple-scattering Monte Carlo UV channel model, addressing weaknesses in previous treatments.

Experimental demonstration of ultraviolet pulse broadening in short-range non-line-of-sight communication channels.

An experimental test-bed using a narrow-pulsed ultraviolet (UV) laser and high-bandwidth photomultiplier tube was set up to characterize pulse broadening effects in short-range non-line-of-sight (NLOS) scattering communication channels. Pulse broadening is reported as a function of the transmitter elevation angle, transmitter beam angle, receiver elevation angle, receiver field-of-view, and transmitter-receiver distance. The results provide insight into the channel bandwidth and achievable communication data rate.

Performance of short-range non-line-of-sight LED-based ultraviolet communication receivers.

Utilizing an empirical path loss model proposed in the first paper of a two-part series, the bit error rate performance of short-range non-line-of-sight ultraviolet communication receivers is analyzed. Typical photodetector models and modulation formats are considered. Our results provide semi-analytical prediction of the achievable communication performance as a function of system and channel parameters, and serve as a basis for system design.

Non-line-of-sight ultraviolet link loss in noncoplanar geometry.

Various path loss models have been developed for solar blind non-line-of-sight UV communication links under an assumption of coplanar source beam axis and receiver pointing direction. This work further extends an existing single-scattering coplanar analytical model to noncoplanar geometry. The model is derived as a function of geometric parameters and atmospheric characteristics.

Path loss modeling and performance trade-off study for short-range non-line-of-sight ultraviolet communications.

We consider outdoor non-line-of-sight deep ultraviolet (UV) solar blind communications at ranges up to 100 m, with different transmitter and receiver geometries. We propose an empirical channel path loss model, and fit the model based on extensive measurements. We observe range-dependent power decay with a power exponent that varies from 0.

Experimental evaluation of LED-based solar blind NLOS communication links.

Experimental results are reported demonstrating non-line of sight short-range ultraviolet communication link losses, and performance of photon counting detectors, operating in the solar blind spectrum regime. We employ light emitting diodes with divergent beams, a solar blind filter, and a wide field-of-view detector. Signal and noise statistics are characterized, and receiver performance is demonstrated.