A physiologically-based recirculatory meta-model for nasal fentanyl in man.

Pharmacokinetic (PK) and pharmacodynamic (PD) data were available from a study of a nasal delivery system for the opioid analgesic fentanyl, together with data on the kinetics of fentanyl in arterial blood in man, and in the lung and brain of sheep. Our aim was to reconcile these data using a physiologically-based population recirculatory PK-PD model, with emphasis on achieving a meta-model that could simultaneously account for the arterial and venous (arm) concentrations of fentanyl, could relate PD effects (pain scores) to the CNS concentrations of fentanyl, and could account for the effect of body size and age on fentanyl kinetics. Data on the concentration gradients of fentanyl across brain, lung and muscle were used to develop sub-models of fentanyl kinetics in these organs.

Serum concentrations of opioids when comparing two switching strategies to methadone for cancer pain.

Purpose: Our aim was to compare pharmacological aspects of two switching strategies from morphine/oxycodone to methadone; the stop and go (SAG) strategy in which methadone is started directly after the initial opioid has been stopped, and the 3-days switch (3DS), in which morphine/oxycodone is gradually changed to methadone by cross-tapering over 3 days.

Methods: Forty-two cancer patients with pain and/or opioid side effects were assessed in this randomised trial. Trough serum concentrations of methadone, morphine, morphine-6-glucuronide (M6G), and oxycodone were measured on days 1, 2, 3, 4, 7, and 14.

European Palliative Care Research Collaborative pain guidelines: opioid switching to improve analgesia or reduce side effects. A systematic review.

According to a Cochrane review on opioid switching, sound evidence on the practice of substituting one strong opioid with another to improve pain control and reduce adverse effects was lacking in 2004. A systematic search strategy was developed to include studies after 2004, with adult cancer patients switching between strong opioids and reporting estimates of effect on pain and adverse effects. The search retrieved 288 publications (71 duplicates); 187 abstracts and 19 full papers were excluded.

Opioid switching to methadone: a pharmacoepidemiological study from a national prescription database.

Background: Opioid switching to methadone is reported frequently to improve pain control in patients with an unacceptable balance between pain control and side effects during treatment with first line opioids, but carries a risk of drug accumulation and respiratory depression. To justify this risk it is required that less risky treatments are tried beforehand and that a sufficiently large proportion of patients experience a long-lasting improvement in pain control.

Research Questions: How large was the proportion of patients remaining on long term methadone treatment after a switch from a strong opioid to methadone? How long had the patients been treated with opioids before the switch to methadone?

Methods: Longitudinal pharmacoepidemiological study from the complete national Norwegian Prescription Database.

Pharmacokinetics of intranasal fentanyl spray in patients with cancer and breakthrough pain.

Objective: This study reports the pharmacokinetics, tolerability, and safety of an intranasalfentanyl spray (INFS) in patients with cancer and breakthrough pain (BTP).

Design: A randomized, open-label, two-period, crossover trial.

Patients: Nineteen adult patients (mean 57.

A double-blind, randomized, crossover comparison between single-dose and double-dose immediate-release oral morphine at bedtime in cancer patients.

The European Association for Palliative Care guidelines for treatment of cancer pain recommend a double dose (DD) of immediate-release morphine at bedtime instead of single doses (SD) repeated every four hours throughout the night. A previous open controlled study reported more side effects after DD than after SD. The present study was a randomized, double-blind, crossover study comparison of DD and SD of immediate-release morphine during the night, followed by an open pharmacokinetic study.

Early pharmacokinetics of nasal fentanyl: is there a significant arterio-venous difference?

Objective: We have investigated the arterio-venous difference in the pharmacokinetics of 50 microg fentanyl during the first hour following nasal administration and documented its tolerability in opioid-naïve middle-aged to elderly patients.

Methods: Twelve male patients (range in age 47-84 years) scheduled for transurethral resection of the prostate gland received a 100-microl dose of 50 microg fentanyl base as a fentanyl citrate formulation in one nostril. Simultaneous arterial and venous blood samples for analyses of fentanyl were drawn at baseline and at 1, 3, 5, 7, 9, 13, 15, 20, 25, 35, 45 and 60 min after drug administration.

[Application of pupillometry and pupillary reactions in medical research].

Background: The iris is a dynamic organ in which the autonomic nervous system regulates the activity. Iris activity reflects physiological reactions to different sensory stimuli, resulting in a variation in pupil size. There are many different diagnostic tools which assess iris activity.