Does Valproic Acid Warrant Therapeutic Drug Monitoring in Bipolar Affective Disorder?

Abstract Objectives Heat treatment is a convenient measure for pathogens inactivation. The authors investigated the effects of this method on blood concentrations of six commonly therapeutic drugs. Methods Plasma and whole blood were pretreated with or without heating at 56 °C for 30 min, and drug concentrations of vancomycin, methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine were examined. Results Increased valproic acid levels after plasma heating (63.2 ± 30.2 vs. 62.1 ± 29.8 mg/L, mean recovery 102.0%) and whole blood heating (64.5 ± 30.5 vs. 62.1 ± 29.8 mg/L, mean recovery 104.6%) were observed (both p<0.05), but these differences were not considered clinically important. Recoveries of vancomycin in heat treatments varied widely, with an average and significant decrease of 15.8% in value after whole blood heating (11.7 ± 8.1 vs. 13.7 ± 8.6 mg/L, p<0.05). Conclusions Plasma or whole blood heating at 56 °C for 30 min are feasible in pathogens inactivation during monitoring methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine. However, such pretreatment seems inappropriate in monitoring vancomycin concentrations. Those results highlight the need for caution when applying heat treatment for pathogens inactivation in therapeutic drug monitoring.

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Development and validation of a new HPLC method for valproic acid determination in human plasma and its application to a therapeutic drug monitoring study

Macedonian Pharmaceutical Bulletin ◽

10.33320/maced.pharm.bull.2020.66.01.001 ◽

2020 ◽

Vol 66 (1) ◽

Author(s):

Emrah Dural ◽

Seniha Çelebi ◽

Aslı Bolayır ◽

Burhanettin Çiğdem

Keyword(s):

Valproic Acid ◽

Therapeutic Drug Monitoring ◽

Human Plasma ◽

Drug Monitoring ◽

High Performance ◽

High Standard ◽

Hplc Method ◽

Therapeutic Drug ◽

Recommended Treatment ◽

Monitoring Study

The aim of this study was to develop a new, simple and reliable high performance liquid chromatography (HPLC) method for analysis of valproic acid (VPA) in human plasma and apply to it to a therapeutic drug monitoring study. Also, the relationship between plasma-VPA concentrations and the amount of VPA used by patients was aimed to be evaluated. Plasma samples (0.25 mL) were precipitated with the same volume of acetonitrile and after centrifugation, aliquots were applied to a C18 column (250 mm x 4.6 mm). Mobile phase was prepared with phosphate buffer and acetonitrile (47.5:52.5, v/v). The flow-rate was 1.2 mL/min. Accuracy was between -2.9 and 3.2% and precision was ≤6.6%. Method was specific and sensitive with a detection limit of 2.2 µg/mL and the average recovery was 94.3%. Calibration curve was linear (r2>0.9968) from 10 to 150 µg/mL. Plasma-VPA levels of the epileptic patient population (n=33) treated with VPA between 0.5 and 1.5 g/day were also determined. Patient plasma-VPA concentrations ranged from 2.9 to 166.4 µg/g/mL (56.3±38.8). High RSD% (68.8%) was observed in dose-rated plasma-VPA results. Moreover, VPA plasma levels were found to be outside the recommended treatment range in 30.3% of the patients examined. The procedure described was found to be relatively simple, precise, and applicable for routine therapeutic drug monitoring (TDM) especially in neurology clinics or in toxicology reference laboratories. The high standard deviation (SD) observed in the dose depended plasma-VPA values of the volunteers proved the importance of TDM during the use of this drug. The results showed that for rational drug use, it is important to identify individual polymorphisms in the CYP2C9, CYP2A6 and CYP2B6 subtypes responsible for VPA metabolism, and to rearrange drug doses taking these enzyme activities into account.

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Simultaneous Determination of Valproic Acid and Its Major Metabolites by UHPLC-MS/MS in Chinese Patients: Application to Therapeutic Drug Monitoring

Journal of Chromatographic Science ◽

10.1093/chromsci/bmw199 ◽

2016 ◽

Cited By ~ 2

Author(s):

Mingming Zhao ◽

Ti Zhang ◽

Guofei Li ◽

Feng Qiu ◽

Yaxin Sun ◽

...

Keyword(s):

Valproic Acid ◽

Therapeutic Drug Monitoring ◽

Simultaneous Determination ◽

Drug Monitoring ◽

Chinese Patients ◽

Therapeutic Drug

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Gas chromatography-electron ionization-mass spectrometry quantitation of valproic acid and gabapentin, using dried plasma spots, for therapeutic drug monitoring in in-home medical care

Biomedical Chromatography ◽

10.1002/bmc.3217 ◽

2014 ◽

Vol 28 (12) ◽

pp. 1756-1762 ◽

Cited By ~ 13

Author(s):

Kayo Ikeda ◽

Kazuro Ikawa ◽

Satoko Yokoshige ◽

Satoshi Yoshikawa ◽

Norifumi Morikawa

Keyword(s):

Mass Spectrometry ◽

Valproic Acid ◽

Gas Chromatography ◽

Therapeutic Drug Monitoring ◽

Medical Care ◽

Drug Monitoring ◽

Electron Ionization Mass Spectrometry ◽

Therapeutic Drug ◽

Ionization Mass ◽

Home Medical Care

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Revisiting the role of therapeutic drug monitoring in optimizing treatment outcomes in patients of bipolar affective disorders receiving lithium therapy: a prospective observational study

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20203064 ◽

2020 ◽

Vol 7 (8) ◽

pp. 1237

Author(s):

Santanu Munshi ◽

Agnik Pal

Keyword(s):

Therapeutic Drug Monitoring ◽

Observational Study ◽

Drug Monitoring ◽

Affective Disorders ◽

Bipolar Affective Disorder ◽

Tertiary Care ◽

Lithium Therapy ◽

Therapeutic Drug ◽

Team Approach ◽

Bipolar Affective Disorders

Background: Lithium continues to be considered first-line therapy for treatment of acute mania, acute mixed bipolar disease and long-term prophylaxis of bipolar disorder. Present study was done to study the pattern of drug therapy in bipolar affective disorder patients with special reference to lithium in the routine psychiatric outpatients care setting of a tertiary care teaching hospital as well as to understand the prospect of therapeutic drug monitoring in optimization of lithium therapy based on outcome.Methods: It was a prospective, non-randomized, observational study of a cohort of subjects who are suffering from bipolar affective disorders and on lithium therapy. Patients were prospectively followed up three monthly for three visits with therapeutic drug monitoring of their plasma lithium level, as and when advised by the treating physician, and pre-formed questionnaires.Results: Results revealed there was significant improvement in symptoms of patients who were monitored with therapeutic drug monitoring and prescribed lithium therapy in accordance with clinical pharmacological consultation for optimal dosing resulting in optimal benefit to patients.Conclusions: With regular therapeutic monitoring, optimal target serum lithium levels can be achieved with dosage modifications thereby reducing the risk of toxicity with improved drug compliance. Thus, individualization of dosing and optimization of treatment can be achieved by dependable analytical laboratory services, better psycho-education, family support and overall a disease-based management team approach with the involvement of clinical Pharmacologist to meet the complexities of lithium therapy.

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