PHARMACOKINETICS OF VANCOMYCIN IN CRITICALLY ILL PATIENTS IN THAILAND

Objective: The pharmacokinetics and pharmacodynamics of drugs in critically ill patients are difficult to predict due to complex pathophysiological changes. Vancomycin is an antibiotic commonly used to treat serious gram positive bacterial infections in critically ill patients and the treatment goal is to rapidly achieve and maintain therapeutic concentrations. We assessed the pharmacokinetics of vancomycin in critically ill patients to help guide dosing.Methods: A total of 138 patients with 299 vancomycin serum concentrations were included in this analysis. Vancomycin serum concentrations were measured using a fluorescence polarization immunoassay. Population pharmacokinetic parameters were estimated using nonlinear mixed effects regression. Age, creatinine clearance (CrCL) and body weight were tested as potential covariates in the pharmacokinetic model.Results: Vancomycin concentration-time profiles were best described by a two-compartment pharmacokinetic model with an additive error model for between subject variability. Creatinine clearance significantly influenced vancomycin clearance (CL). Mean population pharmacokinetic parameters (% between subject variability) were: CL 3.39 l/h (13%), central compartment volume of distribution (V1) 24.92 l (26%); and peripheral compartment volume of distribution (V2) 24.6 (37%).Conclusion: Higher clearance and a smaller volume of distribution of vancomycin was observed in critically-ill patients compared to those reported in non-critically ill patients with a similar distribution of renal function and body weight. Close monitoring of vancomycin serum concentrations is warranted in critically ill patients with dose interval adjustments based on the patient's creatinine clearance.Â

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CROSSOVER STUDY OF CAPPRA® FOR THE TREATMENT OF MILD OR MILD TO MODERATE ERECTILE DYSFUNCTION IN THAI MALE male

Erectile dysfunction (ED) is one of the major health concerns affects the quality of life among Thai male. The treatment of ED by the first-line drugs is limited to a certain group of patients due to their side effects and costs. Alternative medicine can be beneficial for the treatment of ED. This is a randomized, double-blind, placebo-controlled, crossover study aimed to assess the efficacy and safety of Cappra®, a traditional herbal medicine which was used in Thailand for decades, for the treatment of mild and mild to moderate ED in Thai patients. A total of 63 patients with mild or mild to moderate ED were randomized to receive Cappra® or placebo for two weeks in the first period, followed by one week washout period. The patients were switched to the alternative treatment in the second period. The efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire and adverse events. Sixty one patients completed the study. There was an improvement of IIEF score for all domains in Cappra® group compared with placebo group. The mean change of IIEF score from baseline for erectile function domain of Cappra® was significantly higher than placebo (4.87 vs 3.44, p = 0.032). The most common adverse events were dizziness (13.3% Cappra®, 9.6% placebo), face numbness (1.6% Cappra®, 0% placebo), and tachycardia (1.6% Cappra®, 0% placebo). The results from this study demonstrated that Cappra® is effective and well-tolerated and can be used as alternative therapy for mild and mild to moderate ED

Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation

Low-dose rivaroxaban has been used in Asian patients with direct oral anticoagulants (DOACs) eligible for atrial fibrillation (AF). However, there are few pharmacokinetic (PK) data in Thai patients to support precise dosing. This study aimed to develop a population PK model and determine the optimal rivaroxaban doses in Thai patients. A total of 240 Anti-Xa levels of rivaroxaban from 60 Thai patients were analyzed. A population PK model was established using the nonlinear mixed-effect modeling approach. Monte Carlo simulations were used to predict drug exposures at a steady state for various dosages. Proportions of patients having rivaroxaban exposure within typical exposure ranges were determined. A one-compartment model with first-order absorption best described the data. Creatinine clearance (CrCl) and body weight significantly affected CL/F and V/F, respectively. Regardless of body weight, a higher proportion of patients with CrCl < 50 mL/min receiving the 10-mg once-daily dose had rivaroxaban exposures within the typical exposure ranges. In contrast, a higher proportion of patients with CrCl ≥ 50 mL/min receiving the 15-mg once-daily dose had rivaroxaban exposures within the typical exposure ranges. The study’s findings suggested that low-dose rivaroxaban would be better suited for Thai patients and suggested adjusting the medication’s dose in accordance with renal function

Impact of Albumin and Omeprazole on Steady-State Population Pharmacokinetics of Voriconazole and Development of a Voriconazole Dosing Optimization Model in Thai Patients with Hematologic Diseases

This study aimed to identify factors that significantly influence the pharmacokinetics of voriconazole in Thai adults with hematologic diseases, and to determine optimal voriconazole dosing regimens. Blood samples were collected at steady state in 65 patients (237 concentrations) who were taking voriconazole to prevent or treat invasive aspergillosis. The data were analyzed using a nonlinear mixed-effects modeling approach. Monte Carlo simulation was applied to optimize dosage regimens. Data were fitted with the one-compartment model with first-order absorption and elimination. The apparent oral clearance (CL/F) was 3.43 L/h, the apparent volume of distribution (V/F) was 47.6 L, and the absorption rate constant (Ka) was fixed at 1.1 h−1. Albumin and omeprazole ≥ 40 mg/day were found to significantly influence CL/F. The simulation produced the following recommended maintenance doses of voriconazole: 50, 100, and 200 mg every 12 h for albumin levels of 1.5–3, 3.01–4, and 4.01–4.5 g/dL, respectively, in patients who receive omeprazole ≤ 20 mg/day. Patients who receive omeprazole ≥ 40 mg/day and who have serum albumin level 1.5–3 and 3.01–4.5 g/dL should receive voriconazole 50 and 100 mg, every 12 h, respectively. Albumin level and omeprazole dosage should be carefully considered when determining the appropriate dosage of voriconazole in Thai patients