Modeling and Simulations in Latin-American Generic Markets: Perspectives from Chilean Local Industry, Regulatory Agency, and Academia.

In the last 20 years, modeling and simulations (M&S) have gained increased attention in pharmaceutical sciences. International industry and world-reference agencies have used M&S to make cost-efficient decisions through the model-informed drug development (MIDD) framework. Modeling tools include biopredictive dissolution models, physiologically based pharmacokinetic models (PBPK), biopharmaceutic models (PBBM), and virtual bioequivalence, among many others.

Perioperative Acetaminophen Dosing in Obese Children.

Acetaminophen is a commonly used perioperative analgesic drug in children. The use of a preoperative loading dose achieves a target concentration of 10 mg/L associated with a target analgesic effect that is 2.6 pain units (visual analogue scale 1-10).

Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD.

The intravenous induction or loading dose in children is commonly prescribed per kilogram. That dose recognizes the linear relationship between volume of distribution and total body weight. Total body weight comprises both fat and fat-free mass.

Levobupivacaine plasma concentrations following repeat caudal anesthetics.

Aim: A single caudal anesthetic at the start of lower abdominal surgery is unlikely to provide prolonged analgesia. A second caudal at the end of the procedure extends the analgesia duration but total plasma concentrations may be associated with toxicity. Our aim was to measure total plasma levobupivacaine concentrations after repeat caudal anesthesia in infants and to generate a pharmacokinetic model for prediction of plasma concentrations after repeat caudal anesthesia in neonates, infants and children.

Pharmacokinetic Pharmacodynamic Modelling Contributions to Improve Paediatric Anaesthesia Practice.

The use of pharmacokinetic-pharmacodynamic models has improved anaesthesia practice in children through a better understanding of dose-concentration-response relationships, developmental pharmacokinetic changes, quantification of drug interactions and insights into how covariates (e.g., age, size, organ dysfunction, pharmacogenomics) impact drug prescription.

Propofol context-sensitive decrement times in children.

Plasma drug concentration is the variable linking dose to effect. The decrement time required for plasma concentration of anesthetic agents to decrease by 50% (context-sensitive half-time) correlates with the time taken to regain consciousness. However, the decrement time to consciousness may not be 50%.

Pharmacokinetic concepts for dexmedetomidine target-controlled infusion pumps in children.

Pharmacokinetic parameter estimates are used in mathematical equations (pharmacokinetic models) to describe concentration changes with time in a population and are specific to that population. Simulation using these models and their parameter estimates can enrich understanding of drug behavior and serve as a basis for study design. Pharmacokinetic concepts are presented pertaining to future designs of dexmedetomidine target-controlled infusion pumps in children.

Prediction of levobupivacaine concentrations in neonates and infants following neuraxial rescue blocks.

Aim: Pharmacokinetic simulation was used to characterize levobupivacaine disposition after regional anesthetic rescue for failed spinal anesthesia in neonates and infants.

Methods: Population pharmacokinetics of levobupivacaine were estimated after spinal blockade in a cohort of neonates and infants (n = 25, postnatal age 5-18 weeks, gestation 21-41 weeks, weight 2.4-6 kg).

Nebulization of Vancomycin Provides Higher Lung Tissue Concentrations than Intravenous Administration in Ventilated Female Piglets with Healthy Lungs.

Background: Intravenous vancomycin is used to treat ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus, but achieves high rates of failure. Vancomycin nebulization may be efficient to provide high vancomycin lung tissue concentrations. The aim of this study was to compare lung tissue and serum concentrations of vancomycin administered intravenously and by aerosol in mechanically ventilated and anesthetized healthy piglets.

A manual propofol infusion regimen for neonates and infants.

Aims: Manual propofol infusion regimens for neonates and infants have been determined from clinical observations in children under the age of 3 years undergoing anesthesia. We assessed the performance of these regimens using reported age-specific pharmacokinetic parameters for propofol. Where performance was poor, we propose alternative dosing regimens.

Propofol pharmacokinetic and pharmacodynamic profile and its electroencephalographic interaction with remifentanil in children.

Background: Propofol and remifentanil are commonly combined during total intravenous anesthesia. The impact of remifentanil in this relationship is poorly quantified in children. Derivation of an integrated pharmacokinetic and pharmacodynamic propofol model, containing remifentanil pharmacodynamic interaction information, enables propofol effect-site target-controlled infusion in children with a better prediction of its hypnotic effect when both drugs are combined.

Modeling the pharmacokinetics and pharmacodynamics of sevoflurane using compartment models in children and adults.

Background: Sevoflurane pharmacokinetics have been traditionally described using physiological models, while pharmacodynamics employed the use of minimal alveolar concentration.

Aims: The integrated pharmacokinetic-pharmacodynamic relationship of sevoflurane in both adults and children was reviewed using compartment models. We wished to delineate age-related changes in both pharmacokinetics and pharmacodynamics.