Clinical indication for assay request Reasons for sending samples for analysis as documented on assay request forms (more than one reason in some cases) were: P450 inhibitor chemical structure suspected nonadherence (N = 170), baseline concentration during successful therapy (N = 81), confirmation of correct dose (N = 78), suspected drug–drug interaction (N = 14), suspected adverse drug reaction (N = 3) and ‘miscellaneous’ (N = 11). No

quetiapine was detected in 14 (8%) of the ‘suspected nonadherence’ samples and in 69 (9%) of the remaining samples. Where quetiapine was detected the mean (95% CI) plasma quetiapine concentration in the ‘suspected nonadherence’ samples Inhibitors,research,lifescience,medical was significantly lower than in the remaining samples (suspected: 144 [96–535] Inhibitors,research,lifescience,medical μg/l; remaining: 234 [131–977] μg/l; t = 2.6, df = 861, p < 0.01). The mean (95% CI) quetiapine prescribed dose in samples where nonadherence was suspected (566 [600–800] mg/day) was not significantly different from those where adherence was not cited as a reason for the request (620 [600–1200] mg/day). Plasma quetiapine and prescribed dose Inhibitors,research,lifescience,medical Information on prescribed dose was

available for 475 (50%) samples. The mean [95% CI] dose was significantly higher in males as compared with females (641 [600–1240] versus 548 [600–943] mg/day, t = 3.6, df = 446, p < 0.01), although the median dose was the same for both males and females (600 mg/day). The mean [95% CI] plasma quetiapine concentrations in Inhibitors,research,lifescience,medical males (267 [120–962] µg/l) and females (249 [36–839] µg/l) were not significantly different. There was also no significant difference in mean (95% CI) plasma quetiapine concentration between patients aged less than 18 years (277 [38–699] µg/l) and patients aged 65 years or more (235 [11–773] µg/l) when compared with samples from patients aged 18–65 years (241 [13–935] µg/l). Similarly, although nonsmokers had higher mean [95% CI] (234 [104–570] µg/l) plasma Inhibitors,research,lifescience,medical quetiapine concentrations than smokers (180 [83–563] µg/l), this difference

was not statistically significant. For all patients the mean (95% CI) quetiapine dose was 605 (600–1200) and the median (range) 600 (25–1700) mg/day. For 58 (6%) samples (35 patients) the prescribed quetiapine dose was greater than the British National Formulary licensed limit of 800 mg/day (median dose [range] 1200 [850–1700] mg/day) [BNF, 2012]. There was a broad Thiamine-diphosphate kinase relationship between plasma quetiapine and prescribed dose, but there was much variation in plasma quetiapine concentration in each dose band (Table 2). Plasma quetiapine was greater than 2000 µg/l in six samples (six patients). In two samples the dose was given as 600 and 700 mg/day, respectively. Nonadherence was queried in both instances, but no further information was available. Table 2. Plasma quetiapine and prescribed dose (excludes samples in which no quetiapine detected, i.e. quetiapine <5 µg/l).