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.

[Luminescence of Sr2Mg(BO3)2:Tb3+ under vacuum ultraviolet excitation].

The phosphors of Tb3+ activated Sr2 Mg(B03)2 were prepared by high temperature solid-state reaction technique. The phase purity was characterized by the powder X-ray diffraction (XRD). The luminescence properties in VUV-Vis range as well as the decay curves were investigated. The results demonstrate that the band near 178 nm in the VUTV excitation spectra is ascribed to the host-related absorption. The bands of lowest spin-allowed and spin-forbidden f--d transition are located at 235 and 278 nm, respectively. The strongest emission is at 543 nm upon 172 nm excitation and with the color coordinate (0.30, 0.45). The decay time is about 2.8 ms.