Identification of a slow CYP3A4 metabolizer by TDM – a case report

Measuring serum concentrations in patients' blood does not only give information about therapeutic effects but also – and even more so – about individual abnormalities in metabolism or compliance problems. This is possible if the measured concentration is not only referred to the well-known therapeutic reference range but also to a dose-related reference range. The last is calculated with data of clearance, bioavailability, daily dose and interval of taking. We're reporting about a female patient born in 1970, where we measured the serum concentrations of quetiapine several times. Following table shows the course of our results. In all measurings, except for the last one, the quetiapine concentration was 4–8/9fold too high, referred to the respective dose-related reference ranges. In the comedication amitriptyline and in the samples 2, 3 and 4 simvastatine are listed in literature as enzyme inhibitors. However, in our experience these interactions cannot explain the dose-related markedly increased concentrations. That is why we stated a poor metabolizer status for this patient and recommended continuous measuring of serum concentrations. Six weeks after the last very high concentration, another sample was measured. We found a surprisingly weakly increased concentration (just 1.5 fold above the dose-related reference range). Since we expect an increased concentration because of the poor metabolizer status of the patient, we now assume lack of compliance.

Table 1 Blood sampling and quetiapine serum concentrations

Sample	Day of blood sample	Dose [mg]	Expected concentration range [ng/ml]	Measured concentration [ng/ml]
1	11. 03. 2010	600	172–364	1 498
2	19. 03. 2010	500	143–303	1 274
3	26. 03. 2010	300	86–182	679
4	07. 04. 2010	400	115–242	1 108
5	25. 05. 2010	400	115–242	313