Roux-en-Y Gastric Bypass and Antipsychotic Therapeutic Drug Monitoring: Two Cases

2020 ◽  
pp. 089719002090546
Author(s):  
Ian R. McGrane ◽  
Laura A. Salyers ◽  
Jason R. Molinaro ◽  
Robert C. Munjal

Many patients with psychiatric conditions undergo bariatric surgery. The Roux-en-Y gastric bypass (RYGB) procedure alters medication pharmacokinetic properties and may have significant impact on drug response. Our report is the first to describe atypical antipsychotic therapeutic drug monitoring in patients who have undergone RYGB. The first patient is a 53-year-old female with a stable psychiatric condition undergoing a laparoscopic RYGB. Her medications prior and following the procedure include bupropion, fluvoxamine, lurasidone, methylphenidate, oxcarbazepine, and verapamil. A concentration steady-state lurasidone concentration obtained prior to the procedure was 20 ng/mL and returned at 8.1 ng/mL, 29 days after surgery. The second patient is a 42-year-old female psychiatric inpatient who had previously undergone an RYGB procedure. Medications on admission included phenytoin, oxcarbazepine, risperidone, and venlafaxine. The patient was believed to be a good candidate for a long-acting antipsychotic and paliperidone was chosen. After concentration-steady-state on 6 mg oral paliperidone, a 23.5-hour trough level was drawn. The patient was noted to be improved on the oral paliperidone, the paliperidone long-acting injection was given, and the patient was discharged. After discharge, the paliperidone concentration returned very low at 1.1 ng/mL. We describe the contributions of drug–drug interactions, medication release mechanisms, and food coadministration that may have affected our therapeutic drug monitoring. Our therapeutic drug monitoring results need to be replicated prior to use in the general population but suggest that oral extended-release drug formulations are particularly poor choices and that nonoral antipsychotic formulations may be preferred in some patients who have undergone RYBG.

2017 ◽  
Vol 51 (06) ◽  
pp. 270-271 ◽  
Author(s):  
Sara Baldelli ◽  
Emilio Clementi ◽  
Dario Cattaneo

AbstractThe updated AGNP Consensus Guidelines for Therapeutic Drug Monitoring (TDM) in Neuropsychopharmacology recently published in the journal have reinforced the key role of TDM to individualize psychoparmacological therapies in clinical practice. However, we believe, that these guidelines have missed the important opportunity to face with, and to provide useful information on, the emerging issue of long-acting injectable formulations of atypical antipsychotics. Specific therapeutic ranges also for these formulations should be included in the next AGNP guidelines.


2005 ◽  
Vol 18 (6) ◽  
pp. 444-460 ◽  
Author(s):  
Michele Y. Splinter

Eight new antiepileptic drugs (AEDs) have been approved for use within the United States within the past decade. They are felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, and zonisamide. These afford clinicians with more options to increase efficacy and tolerability in the treatment of patients with epilepsy. Pharmacokinetic properties and drug interactions with other AEDs and other medications taken for comorbidities are individually discussed for each of these new agents. Drug concentrations are not routinely monitored for these newer agents, and there have been few studies designed to investigate their concentration-effect relationships. For most of these medications, the concentrations observed in responders and nonresponders overlap considerably and levels associated with efficacy are often associated with adverse events, complicating the definition of target ranges. Also, epilepsy manifests itself sporadically causing difficulty in clinically monitoring efficacy of medications. Therapeutic drug monitoring provides for the individualization of treatment for these agents, which is important because they demonstrate significant variability in inter- and intraindividual pharmaco-kinetic properties. Therapeutic drug monitoring also allows for identification of noncompliance, drug interactions, and toxicity. Current knowledge of the relationships between efficacy, toxicity, and drug concentrations is discussed.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14089-e14089
Author(s):  
Manuel Sureda ◽  
Ana Catalán-Latorre ◽  
Juan José Mata ◽  
Vanesa Escudero ◽  
Antonio Brugarolas

e14089 Background: Fixed dose schemes, regardless of body weight, have been accepted by the regulatory agencies for the PD-1 targeting antibodies. Zaho X. and Ratain M. have elucidated that the mean steady state concentrations of nivolumab (N) at flat-doses of 240 mg Q2W or 480 mg Q4W were 57 µg/mL and 47 µg/mL, respectively. These levels are very similar to those observed at the dosage of 3 mg/kg Q2W. Considering the long half-life of N, its mechanism of action and the absence of correlation between exposure and response or toxicity at clinically tested doses, other schemes can be explored. Moreover, therapeutic drug monitoring (TDM) can contribute to individualize and optimize dosage. We determined serum N levels in patients with solid tumors. Methods: The PK profile of N was analyzed in 15 patients with solid tumors who received 3 mg/kg Q2W from May 2017 through January 2019. Eligible patients had non-small-cell lung cancer (n = 7), urothelial cancer (n = 1), gastric cancer (n = 1), breast cancer (n = 1), renal cell cancer (n = 1), colorectal cancer (n = 1), prostate cancer (n = 1), melanoma (n = 1) and sarcoma (n = 1). Free N serum concentrations were determined with a quantitative ELISA capable of detecting ≥ 0.3 µg/mL (Shikari Q-Nivo, Matriks Biotek, Ankara, Turkey). A total of 28 TDM were done after steady state (6th and 26th cycle). Results: For different reasons, 9 patients received N at 3, 4, 5, 6 or 7 week intervals once the steady state was reached. In these patients, a median reduction of 20.8% (6.7% - 43.0%) of the received doses was observed. Mean plasma concentrations of N observed after administration every 2 weeks was 73.5±32.5 µg/mL (n = 9). Once the steady state was reached, mean plasma concentrations at 3, 4, 5, 6 or 7 weeks, were 54.0±1.3 µg/mL (n = 2), 45.1±25.3 µg/mL (n = 7), 42.9±29.5 µg/mL (n = 5) and 24.4±11.7 µg/mL (n = 5), respectively. No statistically significant differences were observed in the serum levels of N between the dosing intervals of 3, 4 and 5 weeks and the standard regimen (Q2W) (p > 0.05). These data are similar to those described by Long G.V. et al. that compared N pharmacokinetic exposure for the 480 mg Q4W schedule simulated in 3817 patients across multiple tumor types with those for the 3 mg/kg Q2W and 240 mg Q2W schedules. Conclusions: The incorporation of the TDM of N in routine clinical practice could help to maintain a therapeutic drug plasma concentration with lower or less frequent doses, adding a financial benefit, without decreasing clinical efficacy. Further randomized trials to explore alternative dosing schemes of N, including personalization through TDM, are warranted


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