title: Influence of age, gender, body weight and valproate comedication on quetiapine plasma concentrations.
abstract: Quetiapine is a second-generation antipsychotic with a favourable risk/benefit profile that is increasingly used in psychiatric patients. Similar to other antipsychotics, the efficacy and adverse effects of quetiapine depend much more on the actual plasma concentration of the active drug than on the prescribed dose. The present study investigated whether age, gender, body weight or certain comedications influence quetiapine plasma concentration by determining quetiapine plasma levels by tandem mass spectrometry in 94 (36 male and 58 female) patients aged 42.2 +/- 20.0 years. Older age was a significant predictor of a higher quetiapine plasma concentration, with a mean increase of weight-corrected concentration/dose ratio of 11% per 10 years of age (P = 0.003). In females, the concentration/dose (C/D) ratio was 35.4% higher than in males (adjusted mean 0.144 ng/ml/mg for males versus 0.195 ng/ml/mg for females, respectively; P = 0.035). However, after correction for weight, the gender difference in C/D ratio dropped to 22% and significance was lost (P = 0.133). Valproate comedication was associated with a 77% increase in quetiapine plasma levels (P = 0.016). In conclusion, older age, body weight and comedication with valproate have to be considered when prescribing quetiapine. Higher plasma levels in female patients need to be replicated in larger samples.
authors.affiliation: Department of General Psychiatry bDivision of Neurochemistry, Medical University Innsbruck, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Aichhorn
authors.forename: Josef
authors.initials: J
authors.lastname: Marksteiner
authors.forename: Thomas
authors.initials: T
authors.lastname: Walch
authors.forename: Gerald
authors.initials: G
authors.lastname: Zernig
authors.forename: Alois
authors.initials: A
authors.lastname: Saria
authors.forename: Georg
authors.initials: G
authors.lastname: Kemmler
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001835:Body Weight; D003987:Dibenzothiazepines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069348:Quetiapine Fumarate; D012737:Sex Factors; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D014635:Valproic Acid