Studying the relationship between the CYP3A and CYP2D6 probe dextromethorphan and the pharmacokinetics of tamoxifen.

In this observational trial we would like to study the possible correlation between the probe-drug dextromethrophan and tamoxifen pharmacokinetics. In case a good correlation is available, this might help in a stepwise development of truly individualizing tamoxifen treatment. Study objectives are relationships between dextromethorphan clearance and the clearance of tamoxifen in breast cancer patients; relationships between other PK-parameters (AUC, Cmax and Tmax); effects of known polymorphisms in CYP2D6 and CYP3A and other relevant drug metabolizing enzymes and transporters on the pahrmacokinetics of tamoxifen and dextromethorphan. In one center (Erasmus Medical Center at Rotterdam, the netherlands), a total of 37 eligable patients, treated with a dose of 20 or 40 mg of tamoxifen, depending on their indication, will be given 30 mg dextromethorphan orally at day 1. Pharmacokinetic sampling will be performed at given time-points (pre, 30 min-24hours, in total 9 sampling time points). For dextromethorphan, blood samples will be processed to plasma and stored until analysis by a validated liquid chromatography tandem mass spectometry method. For tamoxifen, blood samples will be processed to serum and stored until analysis by a validated liquid chromatography tandem mass spectometry method.

In this observational trial we would like to study the possible correlation between the probe-drug dextromethrophan and tamoxifen pharmacokinetics. In case a good correlation is available, this might help in a stepwise development of truly individualizing tamoxifen treatment.

1. Day -28/-1: informed consent;

2. Day 1: pharmaokinetic sampling (pre, 30 min-24hours in total 9 sampling time points).

Observational study with pharmacokinetic sampling.