A physiological approach to renal clearance: From premature neonates to adults.

Aims: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance.

Methods: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine.

Use of Machine Learning for Dosage Individualization of Vancomycin in Neonates.

Background And Objective: High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C) and steady-state area-under-curve (AUC) targets is important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used to predict these treatment targets to calculate optimal individual dosing regimens under intermittent administration conditions.

Population Pharmacokinetics and Dosing Simulations of Intravenous Oxycodone for Perioperative Pain Relief in Adult Surgical Patients with Obesity.

Background And Objective: Oxycodone, a semisynthetic thebaine derivative µ-opioid (MOP) receptor agonist, is effective for treating moderate and severe pain in different clinical conditions. The pharmacokinetics of intravenous oxycodone in the obese population has not been studied. This study aims to characterize the pharmacokinetic profile of oxycodone after intravenous administration and to simulate an appropriate dosage for analgesic efficacy in obese patients.

Transversus Abdominis Plane Block Versus Intraperitoneal Local Anesthetics in Bariatric Surgery: A Systematic Review and Network Meta-analysis.

Background: Transversus abdominis plane (TAP) block and intraperitoneal local anesthetics (IPLA) are widely investigated techniques that potentially improve analgesia after bariatric surgery. The analgesic efficacy of TAP block has been shown in previous studies, but the performance of TAP block can be difficult in patients with obesity. We performed a systematic review and meta-analysis to compare the analgesic efficacy of TAP block and IPLA.

Drug Clearance in Neonates: A Combination of Population Pharmacokinetic Modelling and Machine Learning Approaches to Improve Individual Prediction.

Background: Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data.

Objective: The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates.

Methods: Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds.

Evaluate construct validity of the Revised American Pain Society Patient Outcome Questionnaire in gynecological postoperative patients using confirmatory factor analysis.

Background: The Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) evaluates the patient-reported quality of pain management in adults. A validated APS-POQ-R is pivotal to guide effective pain management with better patient satisfaction. Previous studies revealed that subscales of "patients' perception of pain management" were unstable cross-culturally.

Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants.

Objectives: In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates.

Methods: A 'meta-model' with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0-24 of 400 mg·h/L at steady-state in at least 80% of neonates.

Results: A two-compartment model best fitted the data.

Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations.

Background And Objectives: Uncertainty exists regarding the optimal dosing regimen for vancomycin in different patient populations, leading to a plethora of subgroup-specific pharmacokinetic models and derived dosing regimens. We aimed to investigate whether a single model for vancomycin could be developed based on a broad dataset covering the extremes of patient characteristics. Furthermore, as a benchmark for current dosing recommendations, we evaluated and optimised the expected vancomycin exposure throughout life and for specific patient subgroups.

Evaluation of the quality of acute pain management in a pediatric surgical setting: Validation of a parent proxy modified version of the revised American Pain Society Patient Outcome Questionnaire.

Background: Effective pain management involves a cycle of continual pain assessment, good pain control strategies, and assessment of a standard quality improvement measures. A validated questionnaire that focuses on the quality of postoperative pain management in pediatric surgical patients and parental satisfaction on pain treatment is lacking. We, therefore, modified the revised American Pain Society Patient Outcome Questionnaire to evaluate the quality of postoperative pain management in a pediatric surgical setting.

Assessment of Predicted Rate and Associated Factors of Dabigatran-induced Bleeding Events in Malaysian Patients with Non-Valvular Atrial Fibrillation.

Purpose: To assess the predicted rate and the factors associated with bleeding events among patients with non-valvular atrial fibrillation (NVAF) receiving dabigatran therapy.

Methods: This retrospective cohort study includes adult patients of two tertiary hospitals in Malaysia. Potential study subjects were identified using pharmacy supply database or novel oral anticoagulant (NOAC) registry.

In vitro inhibitory mechanisms and molecular docking of 1'-S-1'-acetoxychavicol acetate on human cytochrome P450 enzymes.

Background: The compound, 1'-S-1'-acetoxychavicol acetate (ACA), isolated from the rhizomes of a Malaysian ethno-medicinal plant, Alpinia conchigera Griff. (Zingiberaceae), was previously shown to have potential in vivo antitumour activities. In the development of a new drug entity, potential interactions of the compound with the cytochrome P450 superfamily metabolizing enzymes need to be ascertain.

Renal targeting potential of a polymeric drug carrier, poly-l-glutamic acid, in normal and diabetic rats.

Background And Purpose: Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier.

Experimental Approach: H-deoxycytidine-labeled PGs (17 or 41 kDa) and H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats.

Factors associated with abrupt discontinuation of dabigatran therapy in patients with atrial fibrillation in Malaysia.

Background Oral anticoagulant therapy is indicated for the prevention of stroke or other thromboembolic events. Premature discontinuation of oral anticoagulants may increase the risk of thromboembolism resulting in adverse sequelae. There are sparse data on the prevalence and the predictors of dabigatran discontinuation in Malaysian patients with atrial fibrillation.

Rapid and simultaneous quantification of levetiracetam and its carboxylic metabolite in human plasma by liquid chromatography tandem mass spectrometry.

A simple liquid chromatography tandem mass spectrometry method was developed and validated according to the guidelines of the US Food and Drug Administration and the European Medicines Agency for a simultaneous quantification of levetiracetam (LEV) and its metabolite, UCB L057 in the plasma of patients. A 0.050 mL plasma sample was prepared by a simple and direct protein precipitation with 0.

Valproate-induced reversible sensorineural hearing loss: a case report with serial audiometry and pharmacokinetic modelling during a valproate rechallenge.

Hearing loss has been reported with valproic acid (VPA) use. However, this is the first case of VPA-induced hearing loss that was tested and confirmed with a VPA rechallenge, supported by serial audiometry and pharmacokinetic modelling. A 39-year-old truck driver with temporal lobe epilepsy was treated with VPA at 400 mg, twice daily, and developed hearing loss after each dose, but recovered within three hours.

Slow carbamazepine clearance in a nonadherent Malay woman with epilepsy and thyrotoxicosis.

The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control.

External Evaluation of Population Pharmacokinetic Models of Vancomycin in Neonates: The transferability of published models to different clinical settings.

Background: Vancomycin is one of the most evaluated antibiotics in neonates using modeling and simulation approaches. However no clear consensus on optimal dosing has been achieved. The objective of the present study was to perform an external evaluation of published models, in order to test their predictive performances in an independent dataset and to identify the possible study-related factors influencing the transferability of pharmacokinetic models to different clinical settings.

Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination.

The present study determined the pharmacokinetic profile of vancomycin in premature Malaysian infants. A one-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration data (n = 835 points) obtained retrospectively from the drug monitoring records of 116 premature newborn infants. Vancomycin concentrations were estimated by a fluorescence polarization immunoassay.