Dose Optimization of Cefpirome Based on Population Pharmacokinetics and Target Attainment during Extracorporeal Membrane Oxygenation.

To obtain the optimal dosage regimen in patients receiving extracorporeal membrane oxygenation (ECMO), we developed a population pharmacokinetics model for cefpirome and performed pharmacodynamic analyses. This prospective study included 15 patients treated with cefpirome during ECMO. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF) at predose and 0.5 to 1, 2 to 3, 4 to 6, 8 to 10, and 12 h after cefpirome administration. The population pharmacokinetic model was developed using nonlinear mixed effects modeling and stepwise covariate modeling. Monte Carlo simulation was used to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) according to the MIC distribution. Cefpirome pharmacokinetics were best described by a two-compartment model. Covariate analysis indicated that serum creatinine concentration (SCr) was negatively correlated with clearance, and the presence of ECMO increased clearance and the central volume of distribution. The simulations showed that patients with low SCr during ECMO-ON had lower PTA than patients with high SCr during ECMO-OFF; so, a higher dosage of cefpirome was required. Cefpirome of 2 g every 8 h for intravenous bolus injection or 2 g every 12 h for extended infusion over 4 h was recommended with normal kidney function receiving ECMO. We established a population pharmacokinetic model for cefpirome in patients with ECMO, and appropriate cefpirome dosage regimens were recommended. The impact of ECMO could be due to the change in patient status on consideration of the small population and uncertainty in covariate relationships. Dose optimization of cefpirome may improve treatment success and survival in patients receiving ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.).

Hollow Ru/RuO2 nanospheres with nanoparticulate shells for high performance electrocatalytic oxygen evolution reactions.

This work shows that hollow Ru/RuO2 nanoparticles having nanoparticulate shells (HN-Ru/RuO2) can be prepared using hollow microporous organic polymers with Ru species (H-MOP-Ru) as precursors. Using silica spheres as templates, H-MOPs were prepared through the Sonogashira-Hagihara coupling of 1,3,5-triethynylbenzene with 2,3-ethoxymethylenedioxy-1,4-diiodobenzene. Acid hydrolysis of cyclic ethyl orthoformate protecting groups generated catechol moieties to form H-MOP-Cat. Then, H-MOP-Ru was obtained by incorporating Ru species into H-MOP-Cat. Heat-treatment of H-MOP-Ru under air induced the formation of HN-Ru/RuO2 with a diameter of 61 nm and shells consisting of 6-7 nm nanoparticles. Due to the hollow structure and nanoparticulate shells, HN-Ru/RuO2 showed a high surface area of 80 m2 g-1 and a pore volume of 0.18 cm3 g-1. The HN-Ru/RuO2 showed enhanced electrocatalytic performance for the oxygen evolution reaction (OER) with an overpotential of 295 mV @ 10 mA cm-2 and a Tafel slope of 46 mV dec-1 in alkaline electrolyte, compared with control RuO2 such as commercial Ru/RuO2 nanoparticles (A-Ru/RuO2) and home-made Ru/RuO2 nanoparticles (N-Ru/RuO2) prepared via the same synthetic procedure as HN-Ru/RuO2. While HN-Ru/RuO2 inevitably contained Pd originated from coupling catalysts, it showed superior performance to Ru/RuO2 nanoparticles with the same Pd content (N1-Ru/RuO2), indicating that the efficient electrocatalytic performance of HN-Ru/RuO2 is attributable to its hollow structure and nanoparticulate shells.

Dose Optimization of Meropenem in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation in Critically Ill Cardiac Patients: Pharmacokinetic/Pharmacodynamic Modeling.

Background: Our objective was to determine an optimal dosage regimen of meropenem in patients receiving veno-arterial extracorporeal membrane oxygenation (V-A ECMO) by developing a pharmacokinetic/pharmacodynamic (PK/PD) model. Methods: This was a prospective cohort study. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF). The population pharmacokinetic model was developed using nonlinear mixed-effects modeling. A Monte Carlo simulation was used (n = 10,000) to assess the probability of target attainment. Results: Thirteen adult patients on ECMO receiving meropenem were included. Meropenem pharmacokinetics was best fitted by a two-compartment model. The final pharmacokinetic model was: CL (L/h) = 3.79 × 0.44CRRT, central volume of distribution (L) = 2.4, peripheral volume of distribution (L) = 8.56, and intercompartmental clearance (L/h) = 21.3. According to the simulation results, if more aggressive treatment is needed (100% fT > MIC target), dose increment or extended infusion is recommended. Conclusions: We established a population pharmacokinetic model for meropenem in patients receiving V-A ECMO and revealed that it is not necessary to adjust the dosage depending on V-A ECMO. Instead, more aggressive treatment is needed than that of standard treatment, and higher dosage is required without continuous renal replacement therapy (CRRT). Also, extended infusion could lead to better target attainment, and we could provide updated nomograms of the meropenem dosage regimen.

Hydroboration of Hollow Microporous Organic Polymers: A Promising Postsynthetic Modification Method for Functional Materials.

This work shows that hydroboration can be efficiently applied to the postsynthetic modification (PSM) of the Sonogashira-Hagihara coupling-based microporous organic polymers (MOPs). Hollow MOPs (H-MOPs) were prepared by template synthesis through the Sonogashira-Hagihara coupling of tetra(4-ethynylphenyl)methane with 1,4-diiodobenzene. The H-MOPs were used as platforms in the PSM-based functionalization. The heat-treatment of H-MOPs in the presence of a neat pinacolborane reagent resulted in the successful addition of pinacolborane groups to the internal alkynes of H-MOPs, generating H-MOPs with pinacolboranes (H-MOP-BPs). The pinacolborane moieties in the H-MOP-BP were further converted to boronic acid groups. The resultant H-MOP-BAs were used as heterogeneous organocatalysts in the CO2 fixation with epoxides to cyclic carbonates at ambient temperature (50 °C). Moreover, H-MOP-BAs could be recycled with retention of the catalytic performance in five successive reactions.

Room-Temperature Synthesis of a Hollow Microporous Organic Polymer Bearing Activated Alkyne IR Probes for Nonradical Thiol-yne Click-Based Post-Functionalization.

This work shows that hollow microporous organic polymer (H-MOP-A) with activated internal alkynes as IR probes can be prepared by template synthesis based on acyl Sonogashira-Hagihara coupling at room temperature. The H-MOP-A is a versatile platform in the main chain PSM based on nonradical thiol-yne click reaction. Moreover, an IR peak of internal alkynes in the H-MOP-A is very intense and could be utilized in the monitoring of thiol-yne click-based main chain PSM. The functionalized H-MOP-A with carboxylic acids (H-MOP-CA) showed efficient adsorption toward Ag+ ions. The resultant H-MOP-CA-Ag showed excellent performance in the CO2 fixation to α-alkylidene cyclic compounds.

Fe3O4@Void@Microporous Organic Polymer-Based Multifunctional Drug Delivery Systems: Targeting, Imaging, and Magneto-Thermal Behaviors.

Multifunctional drug delivery systems were designed and engineered by template synthesis of a microporous organic polymer (MOP) and by postsynthetic modification. Hollow MOP spheres bearing Fe3O4 yolks (Fe3O4@Void@MOP) were prepared by the synthesis of MOP on Fe3O4@SiO2 nanoparticles and by successive silica etching. In addition to the magneto-thermal function of Fe3O4 yolks, an aggregation-induced emission (AIE) feature was incorporated into the Fe3O4@Void@MOP through a homocoupling of tetra(4-ethynylphenyl)ethylene to form Fe3O4@Void@MOP-TE. Folate groups were further introduced into Fe3O4@Void@MOP-TE through the postsynthetic modification based on the thiol-yne click reaction. The resultant Fe3O4@Void@MOP-TE-FA showed multifunctionality in antitumoral therapy via folate receptor targeting, doxorubicin delivery, AIE-based imaging, and the magneto-thermal feature.

Folate decorated hollow spheres of microporous organic networks as drug delivery materials.

Hollow and microporous organic network spheres decorated with folic acids (H-MON-FA) were prepared using silica templates by the Sonogashira coupling of organic building blocks and successive post-synthetic modifications. The drug (DOX) delivery performance of H-MON-FA to cancer cells was studied.