Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

[Effects of Pesticides Use on Pesticides Residues and Its Environmental Risk Assessment in Xingkai Lake（China）].

Xingkai Lake, located in Heilongjiang Province, is an important fishery and agricultural base and is seriously polluted by agricultural non-point sources. To clarify the residual status of many pesticides in the surface water of Xingkai Lake, 27 types of pesticides, herbicides, and their degradation products were analyzed in rice paddy, drainage, and surface water around Xingkai Lake (China) during the rice heading and maturity periods. The results showed that all 27 types of pesticides, herbicides, and their degradation products were detected during the rice heading period, and the total concentration ranged from 247.97 to 6 094.49 ng·L-1. Additionally, 25 species were detected during the rice maturity period, and the total concentration ranged from 485.36 to 796.23 ng·L-1. In comparison, more pesticides, herbicides, and derived degradation products were detected during the heading period, and their total concentration was higher as well. During the rice heading period, atrazine, simetryn, and paclobutrazol were the main detected pesticides, atrazine and isoprothiolane were the main pesticides detected during the maturity period. The distribution characteristics of pesticides and herbicides in the surface water around Xingkai Lake (China) was similar to that in drainage, so they were probably imported from the drainage and rice paddy. The average risk quotient (RQ) values of atrazine, simetryn, prometryn, butachlor, isoprothiolane, and oxadiazon were higher than 0.1 in drainage and Xingkai Lake (China), which showed a potential risk to aquatic organisms.

Fibrinogen-to-albumin ratio is related to the severity of coronary artery disease in chronic kidney disease patients undergoing coronary angiography / La relación fibrinógeno/albúmina está relacionada con la gravedad de la enfermedad arterial coronaria en pacientes con enfermedad renal crónica tratados mediante a angiografía coronaria

Objectives: This study was to explore the potential relationship between the fibrinogen-to-albumin ratio (FAR) and the presence and severity of coronary artery disease (CAD) in stage 3–5 predialysis chronic kidney disease (CKD) patients.Design: This study included 978 patients undergoing coronary angiography (CAG). CAD was defined as the presence of obstructive stenosis>50% of the lumen diameter in any of the four main coronary arteries. Gensini scores (GSs), left main coronary artery (LMCA) and three-vessel coronary artery disease (TVD) were used to elevate the severity of CAD. Results: The adjusted odds ratios of CAD were 3.059 (95% CI: 1.859–5.032) and 2.670 (95% CI: 1.605–4.441) in the third and fourth quartiles of FAR compared with the first quartile, respectively. Among 759 patients diagnosed with CAD, multivariate logistic regression analysis showed that FAR (at the 0.01 level) was significantly positively associated with the presence of LMCA (adjusted OR=1.177, 95% CI 1.067–1.299, P=0.001) or TVD (adjusted OR=1.154, 95% CI 1.076–1.238, P<0.001), and a higher GS (adjusted OR=1.152, 95% CI 1.073–1.238, P<0.001). Conclusions: FAR levels were independently associated with the presence and severity of CAD in stage 3–5 predialysis CKD patients. (AU)

Objetivos: Este estudio pretendía explorar la relación potencial entre la relación fibrinógeno/albúmina (FAR) y la presencia y la gravedad de la enfermedad arterial coronaria (EAC) en pacientes con enfermedad renal crónica (ERC) en estadio 3-5 en la etapa prediálisis. Diseño: Este estudio incluyó a 978 pacientes tratados mediante angiografía coronaria. La EAC se definió como la presencia de estenosis obstructiva > 50% del diámetro de la luz de cualquiera de las 4 arterias coronarias principales. Se utilizaron las puntuaciones de Gensini (GS), la enfermedad de la arteria coronaria izquierda (EACI) y la EAC de 3 vasos (ETV) para evaluar la gravedad de la EAC. Resultados: Los cocientes de posibilidades de EAC fueron 3,059 (IC del 95%: 1,859-5,032) y 2,670 (IC del 95%: 1,605-4,441) en el tercer y el cuarto cuartiles de la FAR en comparación con el primer cuartil, respectivamente. Entre los 759 pacientes diagnosticados de EAC, el análisis de regresión logística de múltiples variables mostró que la FAR (al nivel 0,01) presentaba una asociación positiva significativa con la presencia de EACI (OR ajustada = 1,177, IC del 95%: 1,067-1,299, p = 0,001) o ETV (OR ajustada=1,154, IC del 95%: 1,076-1,238, p < 0,001) y una puntuación GS mayor (OR ajustada = 1,152, IC del 95%: 1,073-1,238, p < 0,001). Conclusiones: Los niveles de FAR se asociaron de manera independiente con la presencia y la gravedad de EAC en los pacientes con ERC en estadio 3-5 en la etapa prediálisis. (AU)