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Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy

Feng, Y and Gastonguay, MR and Pollock, BG and Frank, E and Kepple, GH and Bies, RR (2011) Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy. Neuropsychiatric Disease and Treatment, 7 (1). 117 - 125. ISSN 1176-6328

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Background: Nonadherence is very common among subjects undergoing pharmacotherapy for schizophrenia and depression. This study aimed to evaluate the performance of the ratio of the nonlinear mixed effects pharmacokinetic model predicted concentration to observed drug concentration (ratio of population predicted to observed concentration (Cpred/Cobs) and ratio of individual predicted to observed concentration (Cipred/Cobs) as a measure of erratic drug exposure, driven primarily by variable execution of the dosage regimen and unknown true dosage history. Methods: Modeling and simulation approaches in conjunction with dosage history information from the Medication Event Monitoring System (MEMS, provided by the "Depression: The search for treatment relevant phenotypes" study), was applied to evaluate the consistency of exposure via simulation studies with scenarios representing a long half-life drug (escitalopram). Adherence rates were calculated based on the percentage of the prescribed doses actually taken correctly during the treatment window of interest. The association between Cpred/Cobs, Cipred/Cobs ratio, and adherence rate was evaluated under various assumptions of known dosing history. Results: Simulations for those scenarios representing a known dosing history were generated from historical MEMS data. Simulations of a long half-life drug exhibited a trend for overprediction of concentrations in patients with a low percentage of doses taken and underprediction of concentrations in patients taking more than their prescribed number of doses. Overall, the ratios did not predict adherence well, except when the true adherence rates were extremely high (greater than 100% of prescribed doses) or extremely low (complete nonadherence). In general, the Cipred/Cobs ratio was a better predictor of adherence rate than the Cpred/Cobs ratio. Correct predictions of extreme (high, low) 7-day adherence rates using Cipred/Cobs were 73.8% and 64.0%. Conclusion: This simulation study demonstrated the limitations of the Cpred/obs and Cipred/obs ratios as metrics for actual dosage intake history, and identified that use of MEMS dosing history monitoring combined with sparse pharmacokinetic sampling is a more reliable approach. © 2011 Feng et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Feng, Y
Gastonguay, MR
Pollock, BG
Frank, E
Kepple, GH
Bies, RR
Date: 1 January 2011
Date Type: Publication
Journal or Publication Title: Neuropsychiatric Disease and Treatment
Volume: 7
Number: 1
Page Range: 117 - 125
DOI or Unique Handle: 10.2147/ndt.s15921
Schools and Programs: School of Medicine > Psychiatry
Refereed: Yes
ISSN: 1176-6328
Date Deposited: 04 Dec 2012 22:39
Last Modified: 21 Dec 2021 11:55


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