19 Therapeutic Reference Ranges of Cariprazine and Atomoxetine

Introduction The effective concentrations of psychotropic drugs should be within the therapeutic reference range. The therapeutic reference range of atomoxetine, has so far only been defined for adult patients between 200–1000 ng/ml. Cariprazine, a second-generation antipsychotic, is indicated for the treatment of schizophrenia. The therapeutic reference range is given as 10–20 ng/ml. The aim in this study is to analyze the pharmacokinetics of atomoxetine and cariprazine more precisely and to re-evaluate recommendations for the therapeutic reference range.

Methods The analytical method for the determination of serum levels of atomoxetine was HPLC/UV. A total of 94 serum atomoxetine levels of 74 children and adolescents were determined and analyzed. Serum levels of cariprazine (CAR) and its pharmacologically active metabolites were quantified using LC-MS/MS.

Results For atomoxetine, maximum serum levels were confirmed in the time window of one to four hours after atomoxetine intake. For the weight normalized dose and the corresponding serum levels a significant correlation according to Pearson was shown (r = 0.807, p = 0.028, n = 7). A preliminary therapeutic reference range for children and adolescents was between 220 and 440 ng/ml. For cariprazine, mean values of 2.7 ng/ml (CAR), 1.6 ng/ml desmethyl-cariprazine and 10.5 ng/ml didesmethyl-cariprazine were measured, maximum values 5.3 ng/ml (CAR), 2.5 ng/ml desmethyl-cariprazine and 18.5 ng/ml didesmethyl-cariprazine.

Conclusion The reference range of atomoxetine for children and adolescents seems to be narrower than for adult patients. In the measurements for cariprazine, the therapeutic reference range established so far was only reached when the sum of the three active compounds was formed.

Publication History

Article published online:
30 April 2020