Drug selection of rapid acting fentanyl formulations in the treatment of breakthrough pain in patients with cancer is performed by the System of Objectified Judgement Analysis method. All seven available formulations were included in the analysis. The following selection criteria were used: number of available strengths, variability in the rate of absorption, interactions, clinical efficacy, side effects, ease of administration and documentation. No direct double-blind comparative studies between two or more formulations were identified and the clinical documentation of all formulations is limited. The most distinguishing criterion was ease of use. This led to slightly higher scores for Abstral, Instanyl and PecFent than for the other formulations. The pros and cons of each formulation should be discussed with the patient, and the most suitable formulation selected for each individual patient.

Purpose: To compare the pharmacodynamic behaviour of vecuronium with that of ORG 9487, we measured the time-course of action of equipotent doses of ORG 9487 and vecuronium and investigated their mutual interaction when given in succession. Methods: Sixty ASA I-II patients were anaesthetized with thiopentone, fentanyl, halothane and nitrous oxide and assigned randomly to four groups. Each patient received an initial dose (ID) of either vecuronium (V) or ORG

We investigated the concentration-time-effect relationship of the relaxant rapacuronium and the contribution of its metabolite. Clearance, rate constant of transport between plasma and the biophase, and modeled concentration in the biophase at 50% effect of rapacuronium are consistent with its rapid onset and short to intermediate duration. The lower clearance of the metabolite will gradually prolong the time course of the neuromuscular blockade during maintenance with rapacuronium.

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A method for simultaneous pharmacokinetic-pharmacodynamic (PK-PD) population analysis using an Iterative Two-Stage Bayesian (ITSB) algorithm was developed. The method was evaluated using clinical data and Monte Carlo simulations. Data from a clinical study with rocuronium in nine anesthetized patients and data generated by Monte Carlo simulation using a similar study design were analysed by sequential PK-PD analysis, PD analysis with nonparametric PK data and simultaneous PK-PD analysis. Both PK and PD data sets were 'rich' with respect to the number of measurements per individual. The accuracy and precision of the estimated population parameters were evaluated by comparing their mean error (ME) and root mean squared error (RMSE), respectively. The influence of PD model misspecification on the results was also investigated. The simultaneous PK-PD analysis resulted in slightly more precise population parameter estimates than the sequential PK-PD analysis and the nonparametric PK method. In the presence of PD model misspecification, however, simultaneous analysis resulted in poor PK parameter estimates, while sequential PK-PD analysis performed well. In conclusion, ITSB is a valuable technique for PK-PD population analysis of rich data sets. The sequential PK-PD method is better suited for the analysis of rich data than the simultaneous analysis.

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