ObjectiveTo investigate the bioavailability of rivastigmine, an approved therapy for patients with mild to moderate dementia of the Alzheimer’s type, at the highest approved single dose of 6mg.Design and settingRandomised, two-period crossover, single-centre, non-blinded, inpatient study.Patients and participantsEleven patients (five females and six males) with mean age 69.5 years.MethodsThe 6mg oral dose was compared with a 2mg intravenous dose of rivastigmine infused over a 1-hour period. Plasma concentrations of rivastigmine and its metabolite NAP 226-90 were measured with a gas chromatographic/mass spectrometric method.ResultsFollowing oral administration of a single 6mg capsule, rivastigmine is rapidly absorbed with an average time to peak plasma concentration of about 1 hour and an average peak concentration of about 25.6 μg/L. By a noncompartmental approach, the absolute bioavailability of the 6mg oral dose of rivastigmine was 71.7% when compared with a 2mg intravenous infusion normalised for dose. By using a population pharmacokinetic model with Michaelis-Menten elimination, absolute bioavailability was estimated at 60.2%. The average terminal elimination half-life of rivastigmine ranged from 1.4 to 1.7 hours for both treatments. Plasma concentrations of the major metabolite, NAP 226-90, formed by the hydrolysis of rivastigmine by cholinesterase are lower than those of the parent compound following oral and intravenous administration.ConclusionA noncompartmental approach and a compartmental approach based on a population pharmacokinetic model with Michaelis-Menten elimination yielded comparable values, 71.7% and 60.2% respectively, for the absolute bioavailability of a single 6mg oral dose of rivastigmine. Comparison with previous studies confirmed that the oral form of the drug exhibits increased bioavailability with increasing dose, consistent with its nonlinear pharmacokinetics.