Population Pharmacokinetics Of Gentamicin In Very Premature Neonates

Gentamicin in combination with benzylpenicillin, is widely used as empiric treatment in early onset neonatal sepsis. The aim of this study is to explore influence of potential covariates on the pharmacokinetic parameters of gentamicin in very premature neonates. A population pharmacokinetic model was developed using NONMEM V (version 1.1). Serum gentamicin concentrations retrospectively collected from […]

An assessment of methods for modelling regional pharmacokinetics – pooled data, pooled parameter estimates or NONMEM?

Aim: Understanding the clinical behaviour of drugs sometimes requires understanding the kinetics (and dynamics) of the drug in its target organ (e.g. the cerebral uptake of anaesthetics and analgesics). One method of studying regional (organ) kinetics is by simultaneously measuring the time-courses of the concentration of the drug in blood entering and leaving the organ. […]

Mechanism-based Pharmacodynamic (PD) Modeling of Phenotypic Tolerance in Pseudomonas aeruginosa for Ceftazidime

Background: Phenotypic tolerance describes the situation in which bacteria are resistant to antibiotics but are genotypically susceptible. Such tolerance may be important for optimal antibiotic therapy. Objectives: 1) To develop a mechanism-based PD model that describes the potential phenotypic tolerance of P. aeruginosa at high initial inocula (CFUo; CFU: colony forming units) to ceftazidime. 2) To propose strategies […]

Lean body weight versus total body weight for propofol dosing

Background: Clinicians have observed longer awakening times for obese compared to normal-weight patients when propofol is dosed as per label guidelines on Total Body Weight (TBW).  This may be explained by the non-linear relationship between TBW and CL described by Schuttler et al1.  Lean Body Weight (LBW) has been reported to have a linear relationship with […]

The evaluation of an individualised dosing strategy derived from population PK modelling and simulation

Background: Recently published enoxaparin dosing guidelines for obese and renally impaired patients are purported to increase the probability of achieving and maintaining anti-Xa (aXa) concentrations within the therapeutic range (TR) of 500-1000 IU/L. Exposure-response data indicate that concentrations greater than the TR increase the risk of bleeding, while concentrations less than the TR increase mortality. Aim: To […]

Population pharmacokinetics of phenobarbitone administered as oral rescue therapy in children with refractory status epilepticus

Background: Parenteral phenobarbitone, used in refractory status epilepticus, was unavailable in South Africafrom 2005 to 2006. Some centres supplemented status epilepticus management with a bolus of nasogastric phenobarbitone for children approaching refractory status. We assessed the efficacy, safety and phenobarbitone pharmacokinetics of this practice. Methods: Patients admitted in status epilepticus were enrolled unless impaired gastric absorption or […]

A model of coagulation disturbances in snake bites

Background: A procoagulant toxin (group C) is found in taipan (Oxyuranus genus) venom, which activates the coagulation cascade and causes venom induced consumptive coagulopathy (VICC). Objectives: To explore the turnover of the clotting factors in the coagulation cascade using a mathematical model and the effects of the procoagulant toxin on this system Evaluate the performance of the […]

Simulation of an optimal pharmacokinetic and pharmacodynamic amikacin dosing regimen for neonates

Objectives: Evaluation of the currently used amikacin dosing regimen in neonates and proposal of an optimal pharmacokinetic (PK) and pharmacodynamic (PD) amikacin dosing regimen. Methods: A retrospective chart review was performed including all neonates treated with amikacin at Dunedin Hospital from Oct 2003 to Jan 2007. The population PK analysis included all the study subjects […]

Modeling Diverse Anti-Diabetic Drug Effects Using Indirect Response Models: Review

Background: Diabetes is a major health risk in many countries and incidence rates are increasing. Diverse anti-diabetic agents act through various mechanisms on different organs. A large array of mathematical models has been proposed to describe anti-diabetic drug effects. Objectives: 1) To systematically compare structural models that were used to model anti-diabetic drug effects. 2) To […]

Optimal design for drug interaction studies – Beyond the criss-cross design

Combination therapies are becoming increasingly common and are standard practice in anesthesia and oncology.  This talk focuses on studies most relevant to anesthesia where it is of interest to describe the pharmacodynamic effect of two drugs given simultaneously.  This effect is generally described via a response surface where parameters exist nonlinearly in the model and […]