Population Pharmacokinetic-Pharmacodynamic Modeling and Probability of Target Attainment Analysis of Rocuronium and Sugammadex in Children Undergoing Surgery.

BACKGROUND AND OBJECTIVES: Probability of target attainment (PTA) curves are commonly used to support dose recommendations of antibiotics for different patient groups. In this study we propose PTA analysis to optimize sugammadex dosing in children. METHODS: This study involved data from an observational cohort study of 30 American Society of Anesthesiologists (ASA) Physical Status I and II children undergoing surgery requiring muscle relaxation. All patients received 0.6 mg/kg rocuronium, with sugammadex administered at the end of surgery in three different doses (0.5, 1.0, and 2.0 mg/kg) to reverse the neuromuscular blockade. RESULTS: The data were analyzed using a population Bayesian-based approach. The developed model was used to simulate pharmacokinetic-pharmacodynamic profiles for different patient groups and dosing regimens before the PTA analysis was performed to translate these simulations into a clinically useful measure. The target was defined as neuromuscular blockade reversal measured by Train-of-Four (TOF ratio > 90%) at 1.5, 3, and 5 min post sugammadex dose. The sugammadex doses leading to 90% PTA were determined for different patients' body weights, rocuronium doses, and time gaps between rocuronium and sugammadex administration assuming the model, priors, and gathered data. For comparison, PTA curves for a range of clinical scenarios are provided to illustrate the usefulness of PTA analysis in selecting the appropriate dose for a given patient. CONCLUSIONS: The proposed PTA analysis is useful to support the sugammadex dose selection in different clinical scenarios. TRIAL REGISTRATION: The study was registered by ClinicalTrials.gov under number NCT04851574 on 21 April 2021.

Comparative study of metals accumulation in cultured in vitro mycelium and naturally grown fruiting bodies of Boletus badius and Cantharellus cibarius.

Cantharellus cibarius Fr. (chanterelle) and Boletus badius Pers. (bay bolete) harvested from natural sites in Poland were used to derive in vitro cultures. The optimal medium composition for cultures was developed. Concentrations of the chosen elements (Zn, Cu, Fe, Mg, Ni, and Cd) in mycelium samples were measured by means of atomic absorption spectrometry. Fe concentration in the analyzed mushroom materials was in the range 215.4-680.3 µg/g dry weight. Mean values of Mg were respectively (in micrograms per gram dry weight) 541.8 for mycelium of C. cibarius cultured in vitro and 1,004.1 for C. cibarius fruiting bodies and 928.9 for the mycelium of B. badius cultured in vitro and 906.4 for B. badius fruiting bodies. The mean concentrations of Zn were 442.7 µg/g dry weight in mycelium from in vitro cultures of B. badius and 172.1 in B. badius fruiting bodies and 131.9 in the case of C. cibarius in mycelium from in vitro cultures and 95.5 for the C. cibarius fruiting bodies. Cu exhibited a reversal tendency, i.e., the element concentrations in naturally grown mushrooms were significantly higher (43.57 µg/g dry weight for C. cibarius and 43.54 µg/g for B. badius) than in cultured in vitro mycelium (12.47 µg/g for C. cibarius and 4.17 µg/g for B. badius). Ni was found in lowest concentrations ranging from 0.33 to 1.88 µg/g dry weight. Toxic metal Cd was found in relatively high concentrations in naturally grown species (0.79 µg/g dry weight-1.02). The lowest was the concentration of Cd in C. cibarius mycelium from in vitro culture-0.06 µg/g dry weight-a bit higher than it was in the B. badius mycelium (0.21 µg/g).