Development of population pharmacokinetics model and Bayesian estimation of rifampicin exposure in Indonesian patients with tuberculosis.

BACKGROUND: Interindividual variability in the pharmacokinetics (PK) of anti-tuberculosis (TB) drugs is the leading cause of treatment failure. Herein, we evaluated the influence of demographic, clinical, and genetic factors that cause variability in RIF PK parameters in Indonesian TB patients. METHODS: In total, 210 Indonesian patients with TB (300 plasma samples) were enrolled in this study. Clinical data, solute carrier organic anion transporter family member-1B1 (SLCO1B1) haplotypes *1a, *1b, and *15, and RIF concentrations were analyzed. The population PK model was developed using a non-linear mixed effect method. RESULTS: A one-compartment model with allometric scaling adequately described the PK of RIF. Age and SLCO1B1 haplotype *15 were significantly associated with variability in apparent clearance (CL/F). For patients in their 40s, each 10-year increase in age was associated with a 10% decrease in CL/F (7.85 L/h). Patients with the SLCO1B1 haplotype *15 had a 24% lower CL/F compared to those with the wild-type. Visual predictive checks and non-parametric bootstrap analysis indicated good model performance. CONCLUSION: Age and SLCO1B1 haplotype *15 were significant covariates of RIF CL/F. Geriatric patients with haplotype *15 had significantly greater exposure to RIF. The model could optimize TB pharmacotherapy through its application in therapeutic drug monitoring (clinical trial no. NCT05280886).

Hyperoxia in the management of respiratory failure: A literature review.

Management of respiratory failure is closely related to oxygen supplementation. Thus, its administration needed special attention according to indications to avoid the toxic effect. Oxygen supplementation in conditions of respiratory failure aims to overcome hypoxemia. Excessive oxygen exposure can cause oxygen toxicity and lead to hyperoxia. Hyperoxia is a condition in which there is an excess supply of oxygen in the tissues and organs. Clinically, respiratory failure is diagnosed if the PaO2 is less than 60 mmHg with or without an increase in carbon dioxide when the patient breathes room air. Respiratory failure is divided into acute (sudden) respiratory failure and chronic (slow) respiratory failure. The basis for managing respiratory failure consists of supportive/non-specific and causative/specific management. Oxygen should be prescribed wisely not to cause injury to organs such as the heart, lungs, eyes, nervous system, and others. Hyperoxia often occurs in managing respiratory failure, so it requires supervision, especially in administering oxygen. Oxygen should be given as needed to avoid hyperoxia. In oxygen therapy, it is necessary to pay attention to the patient's condition because each condition requires different oxygen concentrations, so dose adjustments are necessary. These conditions can be divided into critical, severe, and observation conditions. The target oxygen saturation in all these conditions is 94-98%.