Author Archive | Richard Upton

Aims: A widely exploited feature of the mixed effect modelling software NONMEM (Icon, Ireland) is the ability to model the influence of covariates that change with time within a subject.  It is documented that NONMEM represents the covariate value between TIME1 and TIME2 as the value at COV2 rather than the more intuitive value of […]

Meta-analysis is an established statistical technique closely associated with systematic reviews of the literature. The concepts of a statistical meta-analysis are increasingly applied to pharmacometric analysis (model-based meta-analysis). The common feature of both approaches is that the experimental “unit” is a publication and they seek to address the problem of small sample sizes. The Central […]

Aim: Fentanyl is a potent opioid analgesic used for post-operative management of acute pain and breakthrough cancer pain. During the development of a nasal delivery method for fentanyl, several clinical studies were completed. These included a study of fentanyl delivery via i.v. and nasal routes with venous blood sampling and measurement of post-operative pain scores1, […]

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. […]