Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Clozapine

Geers, Lisanne M; Cohen, Dan; Wehkamp, Laura M; Hateren, Kai van; Koster, Remco A.; Fedorenko, Olga Yu; Semke, A.; Бохан, Н. А.; Ivanova, Svetlana A.; Kosterink, Jos G. W.; Loonen, Anton J. M.; Touw, Daan

doi:10.4088/jcp.16m11164

Cited by 27 publications

(31 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dried blood has been used widely for human and veterinary diagnostic tests. 7,10 Various microsampling devices for collecting blood have become available commercially. Multiplex ICA specifically detected antibodies to HVJ, MHV, and C. piliforme antigens in the presence of whole blood (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Multiplex Immunochromatographic Assay for Serologic Diagnosis of Major Infectious Diseases in Laboratory Mice

Tosa

Ishida

Yoshimatsu

et al. 2019

j am assoc lab anim sci

View full text Add to dashboard Cite

Serologic monitoring of infectious diseases is important for microbial control in colonies of laboratory mice. Rapid and simple tests that do not require killing animals are valuable for this purpose. In this study, we developed a multiplex immunochromatographic assay (ICA) for detection of antibodies to mouse hepatitis virus (MHV), Sendai virus (also known as hemagglutinating virus of Japan [HVJ]), and Clostridium piliforme (The pathogen that causes Tyzzer disease), which are major infectious diseases in mice. For this assay, an ICA strip was put into a microtube containing 150 μL PBS and either 0.75 μL mouse serum or 1.5 μL whole blood. Binding antibodies were visualized by using protein A-conjugated colloidal gold. Under these conditions, multiplex ICA simultaneously and specifically detected antibodies to multiple antigens. To evaluate the sensitivity and specificity of multiplex ICA, positive serum samples for each infectious disease were used. Sensitivities of the multiplex ICA test for MHV, HVJ, and C. piliforme were 100%, 100%, and 90%, respectively. No nonspecific reaction was observed in any of the 30 positive sera. In addition, 10 samples of uninfected sera did not show any bands except for the control line. These observations indicate high specificity of the multiplex ICA test. Moreover, the multiplex ICA could be applied to diluted blood. These results indicate that the multiplex ICA is appropriate for rapid, simple, and safe serologic testing of laboratory mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Multiplex Immunochromatographic Assay for Serologic Diagnosis of Major Infectious Diseases in Laboratory Mice

Tosa

Ishida

Yoshimatsu

et al. 2019

j am assoc lab anim sci

View full text Add to dashboard Cite

show abstract

“…Online supplementary Box S13 [54,155,[229][230][231][232][233][234][235][236][237][238][239][240][241] describes the recent commercialization and/or development of new technologies in pharmacogenetic testing, WBC monitoring, and TDM. The current commercial pharmacogenetic tests should not be used on clozapine patients.…”

Section: Future Use: Technology Advances Coming To Marketmentioning

confidence: 99%

A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology

Leon

Ruan

Schoretsanitis

et al. 2020

Psychother Psychosom

114

113

View full text Add to dashboard Cite

Using Richardson and Davidson's model and the sciences of pharmacokinetics and clinical pharmacopsychology, this article reviewed the: (1) poor life expectancy associated with treatment-resistant schizophrenia (TRS), which may be improved in patients who adhere to clozapine; (2) findings that clozapine is the best treatment for TRS (according to efficacy, effectiveness and well-being); and (3) potential for clozapine to cause vulnerabilities, including potentially lethal adverse drug reactions such as agranulocytosis, pneumonia, and myocarditis. Rational use requires: (1) modification of the clozapine package insert worldwide to include lower doses for Asians and to avoid the lethality associated with pneumonia, (2) the use of clozapine levels for personalizing dosing, and (3) the use of slow and personalized titration. This may make clozapine as safe as possible and contribute to increased life expectancy and well-being. In the absence of data on COVID-19 in clozapine patients, clozapine possibly impairs immunological mechanisms and may increase pneumonia risk in infected patients. Psychiatrists should call their clozapine patients and families and explain to them that if the patient develops fever or flu-like symptoms, the psychiatrist should be called and should consider halving the clozapine dose. If the patient is hospitalized with pneumonia, the treating physician needs to assess for symptoms of clozapine intoxication since halving the dose may not be enough for all patients; consider decreasing it to one-third or even stopping it. Once the signs of inflammation and fever have disappeared, the clozapine dose can be slowly increased to the prior dosage level. 46, 48, 52-67] describes the important pharmacokinetic variables for clozapine clearance. Higher clozapine C/D ratios, indicating lower clearance, are associated with females, non-smokers, Asians, genetic poor metabolizers, inhibitors, obesity, inflammation, and possibly with renal impairment and pregnancy. Lower clozapine C/D ratios indicate lack of adherence or higher clearance associated with males, smokers, non-Asians, and inducers.Two prior TDM review articles [68,69] are summarized in online supplementary Box S3 [31, 44, 50, 51, 55, 58-61, 63, 65, 68-91] which also describe our extensive experience with thousands of inpatient clozapine TDMs under standard conditions (trough and steady-state levels) in the US [44] and China [45,65]. Many of these inpatients were followed for months and/or years after changes in important pharmacokinetic variables [31, 44, 50, 58-61, 63, 65, 74, 79, 86-91].Published review articles [92][93][94] usually insist on the wide variability of clozapine TDM among individuals and the difficulty of interpreting a single clozapine level, but they fail to pay attention to findings from these two sciences: pharmacokinetics and clinical pharmacopsychology, which help in interpreting variability in clozapine levels. In inpatients, repeated measures allow the calculation of average clozapine clearance in an individual through a...

show abstract

“…Box describes the areas needing further study including (a) Asian CLO therapeutic reference range in schizophrenia, (b) Asian CLO dosing and TDM in other indications, (c) Asian CLO titration and myocarditis, (d) identification of mutations that may explain Asian CLO PMs, (e) CLO dosing in Western Asians, (f) NCLO TDM, (g) CLO/NCLO ratio, (h) N‐CLO‐oxide TDM (de Leon & Simpson, ; Kikuchi et al, ; Li et al, ; Otsuka et al, ; Ronaldson et al, ; Schoretsanitis et al, ; Ye et al, ), and (i) dried blood spot technology (Geers et al, ; Nakahara et al, ; Temesi et al, ).…”

Section: Areas Needing Further Studymentioning

confidence: 99%

Using therapeutic drug monitoring to personalize clozapine dosing in Asians

Leon

Schoretsanitis

Kane

et al. 2020

Asia-Pacific Psychiatry

View full text Add to dashboard Cite

This narrative review on clozapine blood levels or therapeutic drug monitoring (TDM) includes sections focused on drug clearance and TDM, personalized dosing with TDM, clinical applications of TDM in Asians, and areas needing further study. Asian patients need half the clozapine dose (D) used in the United States to get the same blood concentrations (C). The concentration-to-dose (C/D) ratio measures drug clearance. In the United States, the average clozapine patient usually needs from 300 to 600 mg/day to reach 350 ng/mL. US male smokers reach this therapeutic C with a D of 600 mg/day (C/D ratio of 0.60 = 600/350), whereas US female nonsmokers usually need a D of 300 mg/day (C/D ratio of 1.17 = 300/350). While in the United States, average CLO C/D ratios typically are 0.6-1.2 ng/mL per mg/day, in Asian populations they range from 1.20 in male smokers to 2.40 in female smokers, requiring Ds of 300 to 150 mg/day to obtain 350 ng/mL. Asian patients can become clozapine poor metabolizers (PMs), needing very low Ds (50-150 mg/day) to get therapeutic Cs, by taking inhibitors (fluvoxamine, oral contraceptives and valproic acid), due to obesity, or duringinflammations with systemic effects. In 573 Asian patients from five samples, around 1% were PMs due to taking inhibitors, 1% due to inflammation, 1% due to obesity, and 7% were potential genetic PMs. The potential genetic PMs ranged between 3% and 13%, but this prevalence will have to be better established in future studies including genetic testing for possible CYP1A2 mutations, which may explain PM status. K E Y W O R D Sclozapine blood, drug interactions, inflammation, sex, smoking

show abstract

Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Clozapine

Abstract: DBS analysis is a reliable tool for blood sampling and performing TDM of clozapine and norclozapine in daily practice and substantially extends the opportunities for TDM of clozapine.

Cited by 27 publications

References 24 publications

Multiplex Immunochromatographic Assay for Serologic Diagnosis of Major Infectious Diseases in Laboratory Mice

Multiplex Immunochromatographic Assay for Serologic Diagnosis of Major Infectious Diseases in Laboratory Mice

A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology

Using therapeutic drug monitoring to personalize clozapine dosing in Asians

Contact Info

Product

Resources

About