Pharmacokinetics and effects of formoterol fumarate in healthy human subjects after oral dosing.

Objective: To evaluate the effects of formoterol after oral administration on plasma eosinophils and plasma potassium in healthy subjects.

Methods: Plasma concentrations of formoterol, peripheral eosinophil count and plasma potassium were determined during 7 h after oral administration of 168 microg of formoterol to eight healthy subjects. Descriptions of the concentration-time course of formoterol are given using a one-compartment pharmacokinetic model with first-order absorption in four subjects and a two-compartment model in the other four subjects.

Some observations on pharmacoepidemiology in Europe.

The need for pharmacoepidemiology, defined as the study of the use of and the effects of drugs in large numbers of people, will increase exponentially in the next decade both in developed and in developing countries. Within Europe, a common market of over 350 million consumers, regulations and guidelines related to drug use were formulated, especially with respect to post-marketing surveillance and the detection, interpretation and management of rare but serious drug related adverse events. The activities of international organizations like the World Health Organization in this context are briefly addressed.

Biphasic effect-time courses in man after formoterol inhalation: eosinopenic and hypokalemic effects and inhibition of allergic skin reactions.

The kinetics of inhaled racemic formoterol and its effects on the size of the early cutaneous reaction to intradermal injection of an allergen, eosinopenia and hypokalemia were assessed by pharmacokinetic-pharmacodynamic modeling. After inhalation of either 120 microg of formoterol or placebo, blood samples were taken and skin tests were performed in seven healthy subjects. A two-compartment model was needed to describe the observed formoterol plasma concentration-time curves.

Evaluation of different doses of formoterol from a newly developed powder inhalation device in asthmatic patients.

Administration of different doses of formoterol from a recently developed multiple dose dry powder device was tested in a placebo-controlled, single-centre, double-blind, within-patient trial. Eighteen patients of both sexes, aged 18-65 years, with a FEV1 of 50-80% and a reversibility of at least 15% were randomized. During four treatment periods of 8 days each, divided by approximately 6 days, patients received placebo or 6, 12 or 24 micrograms (PL, F6, F12 and F24, respectively) of formoterol from the powder device.

Enhanced differential diagnosis of anticonvulsant hypersensitivity reactions by an integrated Bayesian and biochemical approach.

Objective: The differential diagnosis of hypersensitivity reactions associated with anticonvulsants requires accuracy because of the many implications for patient management. We tested an integrated Bayesian and biochemical diagnostic approach.

Methods: The patients were analyzed clinically by two tests.

Computer-assisted evaluation of adverse events using a Bayesian approach.

The differential diagnosis of idiosyncratic adverse drug reactions (ADRs) is complex because for each adverse event there are many possible drug and nondrug causes. Recently efforts have been made to computerize causality assessment methods. A new computerized, user-friendly diagnostic aid for Bayesian assessment of adverse drug events (MacBARDI-Q&A) is described.

Behavioural correlates of alcohol intoxication.

Alcohol is used in most cultures despite knowledge of the physical, psychological and social problems associated with its abuse. Behavioural impairment is a function of several factors, including blood alcohol concentration (BAC) and the rate of alcohol metabolism by alcohol dehydrogenase and the microsomal ethanol-oxidizing system. Their availability and activity depend upon alcohol use history, ethnicity, other drug use and gender.

Clinical pharmacology of serotonin-altering medications for decreasing alcohol consumption.

Variations in serotonin neurotransmission influence alcohol consumption (AC). Levels of 5-HT and metabolites are low in some brain regions of alcohol preferring rats and in CSF of alcoholics. Pharmacological treatments which enhance serotonergic neurotransmission (uptake inhibitors, releasers, agonists) consistently reduce AC in rats.