scholarly journals Adverse Outcomes in Pulmonary Tuberculosis patients on Retreatment Regimen: Evaluation of Pharmacokinetic Estimates as Risk Indicators

2021 ◽  
Author(s):  
Anant Mohan ◽  
Anuuj K Bhatnagar ◽  
Tarang Gupta ◽  
Sunita Kanswal ◽  
Ujjalkumar Das ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Pulmonary Tuberculosis ◽  
Plasma Levels ◽  
Geometric Mean ◽  
Adverse Outcomes ◽  
Risk Indicators ◽  
Therapeutic Drug ◽  
Plasma Drug ◽  
Drug Levels ◽  
Plasma Drug Levels

Patients with pulmonary tuberculosis (PTB) who fail therapy or develop a relapse are initiated on re-treatment regimen. These patients are known to have adverse outcomes. This study aimed to determine the role of plasma levels of Anti-tubercular drugs in treatment outcome. Plasma levels of retreatment regimen drugs [Isoniazid(INH), Rifampicin(RIF), Pyrazinamide(PZA), Ethambutol(EMB), and Streptomycin(STM)] were compared between treatment responsive/cured and treatment failure/not-cured patients. Plasma drug levels were analysed by LC-MS/MS at different time points in 134 PTB patients on retreatment regimen. Of the 134 subjects, 108 were cured, 17 patients developed multi-drug resistant TB (MDR-TB), and 9 patients remained smear positive at treatment completion (8 months). The two-hour plasma levels (C2hr) (geometric mean) were lower in 'Not Cured' subjects compared to 'Cured' subjects Notably, in the 26 'Not Cured' subjects, C2hr plasma levels after first dose at Day0 were significantly low (INH: 0.86 vs 2.94 μg/ml p≤0.002, RIF: 0.56 vs 2.55 μg/ml p≤0.003, PZA: 1.85 vs 26.58 μg/ml p≤0.000 and EMB: 0.72 vs 1.53 μg/ml p≤0.010). In contrast, STM levels were higher (31.84 vs 18.08 μg/ml p ≤0.007). Based on ROC analysis of the data, therapeutic indicator values for successful treatment outcome were C2hr plasma levels of 10.6 μg/ml for PZA, 1.14 &mug/ml for RIF, 1.86 μg/ml for INH and 1.24 μg/ml for EMB. Therapeutic failure in PTB patients on retreatment regimen is associated with lower plasma drug levels. Therapeutic drug monitoring would prove useful to maintain drug levels above the minimum cut-off levels for obtaining favorable clinical outcome.

scholarly journals Antifungal Efficacy, Safety, and Single-Dose Pharmacokinetics of LY303366, a Novel Echinocandin B, in Experimental Pulmonary Aspergillosis in Persistently Neutropenic Rabbits

1998 ◽  
Vol 42 (11) ◽  
pp. 2898-2905 ◽  
Author(s):  
Vidmantas Petraitis ◽  
Ruta Petraitiene ◽  
Andreas H. Groll ◽  
Aaron Bell ◽  
Diana P. Callender ◽  
...  
Keyword(s):  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Injury ◽  
Plasma Drug ◽  
Pulmonary Aspergillosis ◽  
Time Curve ◽  
Drug Levels ◽  
Plasma Drug Levels ◽  
Echinocandin B ◽  
Improvement In Survival ◽  
Antifungal Efficacy

ABSTRACT LY303366 is a novel semisynthetic derivative of echinocandin B and a potent inhibitor of fungal (1,3)-β-d-glucan synthase. The antifungal efficacy and safety of LY303366 were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due toAspergillus fumigatus in persistently neutropenic rabbits. Treatment study groups were either not treated (controls) or treated with amphotericin B (AmB) at 1 mg/kg of body weight per day or with LY303366 at 1, 5, 10, and 20 mg/kg/day. In rabbits treated with LY303366, there was a significant improvement in survival and a reduction in organism-mediated pulmonary injury measured by the number of infarcts, total lung weight, and ultrafast computerized tomography scan pulmonary lesion score. Rabbits receiving prophylactic LY303366 also demonstrated significant improvement in survival and reduction in organism-mediated pulmonary injury. AmB and LY303366 had comparable therapeutic efficacies by all parameters with the exception of reduction in tissue burden ofA. fumigatus, where AmB was superior to LY303366. LY303366 demonstrated a dose-dependent effect on hyphal injury with progressive truncation, swelling, and vacuolization. LY303366 administered in single doses of 1, 5, 10, and 20 mg/kg demonstrated dose-proportional increases in the maximum concentration of drug in plasma and the area under the concentration-time curve from 0 to 72 h with no changes in plasma drug clearance. The 1-mg/kg dosage maintained plasma drug levels above the MIC for 18 h, and dosages of ≥5 mg/kg maintained plasma drug levels above the MIC for the entire 24-h dosing interval. There was no significant elevation of the concentrations of hepatic transaminases or creatinine in serum in LY303366-treated rabbits. In summary, LY303366 improved survival and decreased pulmonary injury with no apparent toxicity in the treatment and prevention of invasive pulmonary aspergillosis in persistently neutropenic rabbits.

scholarly journals Extended cell and plasma drug levels after one dose of a three-in-one nanosuspension containing lopinavir, efavirenz, and tenofovir in nonhuman primates

AIDS ◽  
2018 ◽  
Vol 32 (17) ◽  
pp. 2463-2467 ◽  
Author(s):  
Josefin Koehn ◽  
Jennifer F. Iwamoto ◽  
John C. Kraft ◽  
Lisa A. McConnachie ◽  
Ann C. Collier ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Plasma Drug ◽  
Drug Levels ◽  
Plasma Drug Levels

scholarly journals Therapeutic Drug Monitoring of Piperacillin-Tazobactam Using Spent Dialysate Effluent in Patients Receiving Continuous Venovenous Hemodialysis

2010 ◽  
Vol 55 (2) ◽  
pp. 557-560 ◽  
Author(s):  
Michael J. Connor ◽  
Charbel Salem ◽  
Seth R. Bauer ◽  
Christina L. Hofmann ◽  
Joseph Groszek ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Kidney Injury ◽  
Therapeutic Drug ◽  
Plasma Drug ◽  
Drug Dosing ◽  
Drug Levels ◽  
Drug Concentrations ◽  
Continuous Venovenous Hemodialysis ◽  
Dosing Strategies

ABSTRACTSepsis and multisystem organ failure are common diagnoses affecting nearly three-quarters of a million Americans annually. Infection is the leading cause of death in acute kidney injury, and the majority of critically ill patients who receive continuous dialysis also receive antibiotics. Dialysis equipment and prescriptions have gradually changed over time, raising concern that current drug dosing recommendations in the literature may result in underdosing of antibiotics. Our research group directed its attention toward antibiotic dosing strategies in patients with acute renal failure (ARF), and we sought data confirming that patients receiving continuous dialysis and antibiotics actually were achieving therapeutic plasma drug levels during treatment. In the course of those investigations, we explored “fast-track” strategies to estimate plasma drug concentrations. As most antimicrobial antibiotics are small molecules and should pass freely through modern high-flux hemodialyzer filters, we hypothesized that continuous renal replacement therapy (CRRT) effluent could be used as the medium for drug concentration measurement by reverse-phase high-pressure liquid chromatography (HPLC). Here we present the first data demonstrating this approach for piperacillin-tazobactam. Paired blood and dialysate trough-peak-trough samples were drawn from 19 patients receiving piperacillin-tazobactam and continuous venovenous hemodialysis (CVVHD). Total, free, and dialysate drug concentrations were measured by HPLC. Dialysate drug levels predicted plasma free drug levels well (r2= 0.91 and 0.92 for piperacillin and tazobactam, respectively) in all patients. These data suggest a strategy for therapeutic drug monitoring that minimizes blood loss from phlebotomy and simplifies analytic procedures.

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