Pharmacokinetics and Monte Carlo Dosing Simulations of Imipenem in Critically Ill Patients with Life-Threatening Severe Infections During Support with Extracorporeal Membrane Oxygenation.

Background: Extracorporeal membrane oxygenation (ECMO), a cardiopulmonary bypass device, has been found to increase the profound pathophysiological changes associated with life-threatening severe infections in patients with multiple comorbidities, which results in alterations of pharmacokinetic patterns for antibiotics.

Objectives: The aims of this study were (1) to determine the pharmacokinetics of imipenem and (2) to assess the probability of target attainment (PTA) for imipenem in critically ill patients with life-threatening severe infections during support with ECMO.

Methods: The pharmacokinetic studies were carried out following administration of 0.

Prediction Of Serum Digoxin Concentration Using Estimated Glomerular Filtration Rate In Thai Population.

Purpose: Serum digoxin concentration (SDC) monitoring may be unavailable in some healthcare settings. Predicted SDC comes into play in the efficacy and toxicity monitoring of digoxin. Renal function is the important parameter for predicting SDC.

Population pharmacokinetics and Monte Carlo simulations of sulbactam to optimize dosage regimens in patients with ventilator-associated pneumonia caused by Acinetobacter baumannii.

Background: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Acinetobacter baumannii remains one of the leading causes of the high mortality rate in critically ill patients. Sulbactam has been considered as an alternative concomitant medication with other effective antimicrobial agents for the treatment of these MDR microorganisms. The aims of this study were (i) to characterize the population pharmacokinetics (PK) and (ii) to assess the efficacy of various dosage regimens of sulbactam in terms of probability of target attainment (PTA).

Population Pharmacokinetics and Pharmacodynamics Modeling of Oral Levofloxacin.

Background: Levofloxacin, a fluoroquinolone, is an isomer of ofloxacin with an extensive spectrum of antimicrobial efficacy. In common with other fluoroquinolones, the main pharmacokinetic/pharmacodynamic (PK/PD) index that correlates with its therapeutic efficacy is the area under the plasma time-concentration curve (AUC)/the minimum inhibitory concentration (MIC) ratios.

Objective: To evaluate the population PK and determine the efficacy of various dosage regimens in achieving the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of oral levofloxacin when prescribed as the switching therapy after intravenous levofloxacin treatment.

The pharmacokinetics of vancomycin during the initial loading dose in patients with septic shock.

Objective: To characterize the pharmacokinetics (PK) of vancomycin in patients in the initial phase of septic shock.

Methods: Twelve patients with septic shock received an intravenous infusion of vancomycin 30 mg/kg over 2 h. The vancomycin PK study was conducted during the first 12 h of the regimen.

Population Pharmacokinetics and Pharmacodynamics Modeling To Optimize Dosage Regimens of Sulbactam in Critically Ill Patients with Severe Sepsis Caused by Acinetobacter baumannii.

Sulbactam is being considered as an alternative concomitant medication with other effective antibiotics for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections. Pathophysiological changes in critically ill patients with severe sepsis, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors in determining therapeutic success. The aims of this study were (i) to examine the population PK parameters and (ii) to assess the probability of target attainment (PTA) for sulbactam in patients with severe sepsis caused by A.

Vancomycin Dosing Regimen by Monte Carlo Simulation in Patients on Intermittent High-Efficiency Hemodialysis (HEHD).

Objective: To evaluate the effective vancomycin dosing regimens by Monte Carlo simulation among patients on intermittent high-efficiency hemodialysis (HEHD).

Material And Method: The present study was conducted on eight end-stage renal disease patients receiving HEHD. The patients received an initial dose of vancomycin 1 g followedby 500 mg immediately after HEHD session for a supplementation.

Population pharmacokinetics and Monte Carlo dosing simulations of meropenem during the early phase of severe sepsis and septic shock in critically ill patients in intensive care units.

Pathophysiological changes during the early phase of severe sepsis and septic shock in critically ill patients, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors influencing therapeutic success. The aims of this study were (i) to reveal the population PK parameters and (ii) to assess the probability of target attainment (PTA) for meropenem. The PK studies were carried out following administration of 1 g of meropenem every 8 h during the first 24 h of severe sepsis and septic shock in nine patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the free plasma drug concentration remains above the MIC (fT>MIC) and 80% fT>MIC.

Population pharmacokinetics and dosing simulations of imipenem in serious bacteraemia in immunocompromised patients with febrile neutropenia.

The aims of this study were to i) reveal the population pharmacokinetics; and ii) assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) (defined as the expected population PTA for a specific drug dose and a specific population of microorganisms) of imipenem in febrile neutropenic patients with bacteraemia. Ten patients were randomised into two groups: Group I received a 0.5-h infusion of 0.

Initial dosage regimen of vancomycin for septic shock patients: a pharmacokinetic study and Monte Carlo simulation.

Objective: To evaluate the pharmacokinetic parameters of vancomycin in septic shock patients and to determine the vancomycin dosage to achieve requisite pharmacokinetic/pharmacodynamic (PK/PD) target against methicillin resistant Staphylocccus aureus (MRSA) in patients with septic shock.

Material And Method: Pharmacokinetic parameters of vancomycin in 12 septic shock patients were assessed. Then, the Monte Carlo simulation was performed to calculate the probabilities of target attainment (PTAs) to reach target AUC0-24/MIC of 400 and 450 mg.

Evaluation of nicotinamide microemulsion on the skin penetration enhancement.

This study purposed to evaluate a microemulsion containing nicotinamide for its characteristics, stability, and skin penetration and retention comparing with a solution of nicotinamide in 2:1 mixture of water and isopropyl alcohol (IPA). The microemulsion system was composed of 1:1 mixture of Span80 and Tween80 as a surfactant mixture, isopropyl palmitate (IPP) as an oil phase, and 2:1 mixture of water and IPA as an aqueous phase. Nicotinamide microemulsion was prepared by dissolving the active in the aqueous phase before simply mixing with the other components.

Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance.

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices.

Pharmacodynamics of meropenem in critically ill patients with ventilator-associated pneumonia.

Background: Pharmacokinetic changes have been found in critically ill patients, including ventilator-associated pneumonia (VAP) when compared with healthy volunteers leading to fluctuation of plasma concentrations.

Objective: To compare the probability of target attainment (PTA) and cumulative fraction of response (CFR) for meropenem between administration by a bolus injection and a 3-hour infusion.

Material And Method: The study was a randomized three-way crossover in nine patients with VAP.

Pharmacodynamics of imipenem in critically ill patients with ventilator-associated pneumonia.

Background: Drug dispositions are altered in critically ill patients, including ventilator-associated pneumonia (VAP) when compared with healthy subjects leading to fluctuations of plasma concentrations.

Objective: To compare the probability of target attainment (PTA) and cumulative fraction of response (CFR) for imipenem between administration by 0.5-hour and 2-hour infusions.

Pharmacodynamics modeling to optimize dosage regimens of sulbactam.

The aim of this study was to reveal population pharmacokinetics and assess the efficacies of various dosage regimens of sulbactam in terms of the probability of target attainment with this agent over a range of MICs. Monte Carlo simulations were performed to determine the probability of attaining specific pharmacodynamic targets. The results indicated that a regimen consisting of a 4-h infusion of 3 g of sulbactam every 8 h would be an alternative treatment option for less-susceptible pathogens.

Pharmacodynamics of doripenem in critically ill patients with ventilator-associated Gram-negative bacilli pneumonia.

Several pathophysiological changes in critically ill patients are important in determining the therapeutic success of β-lactam antibiotics. The aim of this study was to assess the population pharmacokinetics and probabilities of target attainment (PTAs) of doripenem in patients with ventilator-associated pneumonia, comparing administration by 1-h and 4-h infusion. Patients were randomised into two groups: Group I received a 1-h infusion of 0.

Pharmacodynamics of meropenem in critically ill patients with febrile neutropenia and bacteraemia.

The bactericidal activity of β-lactams is determined by the time that concentrations in tissue and serum are above the minimum inhibitory concentration (T>MIC) for the pathogen. The aim of this study was to compare the probability of target attainment (PTA) and the cumulative fraction of response (CFR) for meropenem between administration by bolus injection and a 3-h infusion. The study was a randomised, three-way, cross-over design in eight febrile neutropenic patients with bacteraemia.

Prediction of solubility parameters using partial least square regression.

The total solubility parameter (delta) values were effectively predicted by using computed molecular descriptors and multivariate partial least squares (PLS) statistics. The molecular descriptors in the derived models included heat of formation, dipole moment, molar refractivity, solvent-accessible surface area (SA), surface-bounded molecular volume (SV), unsaturated index (Ui), and hydrophilic index (Hy). The values of these descriptors were computed by the use of HyperChem 7.

Formulation and efficacy of triamcinolone acetonide mouthwash for treating oral lichen planus.

Purpose: The stability of a triamcinolone acetonide mouthwash and its efficacy in treating oral lichen planus are described.

Methods: The solubility of triamcinolone acetonide in ethanol, propylene glycol, and glycerin was determined by shaking and equilibrating an excess of triamcinolone acetonide with the solvents for 72 hours. All three solvents were used in formulating a mouthwash.

Optimization in development of acetaminophen syrup formulation.

Formulation of acetaminophen syrup could be developed by an optimization technique to reduce the time and cost of study. Cosolvents were used in the formulation because of the low solubility of acetaminophen in water. They were composed of polyethylene glycol 4000, propylene glycol, sorbitol solution, and glycerin.

Unified algorithm for real-time detection of drug interaction and drug allergy.

This algorithm aims at unifying and generalizing the algorithm for detecting all types of documented drug interactions such as drug-drug interactions, drug-disease interactions, drug-patient interactions (drug allergy) from patient profile information and drug-laboratory test interactions in real-time prescribing system. Ideally, the system should conform to the following criteria: (1) data independence; (2) software interconnectability; (3) knowledge expandability; (4) flexibility; and (5) computation resource efficiency. We propose a robust Structured Query Language (SQL) algorithm to detect drug interactions and drug allergy according to such criteria.