The study patients' pharmacokinetic parameters will be estimated by a Bayesian procedure based on a population model, according to methods already in use e.g. for aminoglycoside antibiotics, digoxin or immunomodulating drugs. Pharmacokinetic parameter estimates will be obtained from the 6 month results and then be updated when new data is obtained after 9, 12, 15 and 18 months. A complete population pharmacokinetic analysis will be performed after collection of all data with the aim to investigate: