Clinical Pharmacogenetics Laboratory

At Üsküdar University’s Medical Genetics and Molecular Diagnostics Laboratory, genotyping studies are conducted to determine individuals’ pharmacogenetic profiles. Our laboratory has been designed to accommodate studies at the molecular level and is equipped with the necessary machinery and equipment, forming a fully-fledged Medical Genetics and Molecular Diagnostics laboratory.

In our laboratory, we isolate DNA or RNA from blood or any tissue samples collected from patients to enable genotyping. These samples can then be used for genotyping or to determine expression levels. For genotyping studies, we perform conventional PCR (polymerase chain reaction), restriction enzyme fragment length polymorphism (RFLP) analysis, and sequencing. In addition, our laboratory conducts more precise analyses using real-time PCR.

Genotyping studies sometimes complement phenotypic studies and, in other cases, serve as a precursor to them. By establishing a genotype-phenotype correlation, we are able to implement a treatment program for patients that is more effective, delivered in a shorter timeframe, and with minimized side effects. Genotypic analyses of the CYP2D6, CYP2C9, CYP2C19, CYP1A2, and CYP3A4 groups, as well as 5HTT and COMT polymorphisms, are the primary genes genotyped.

What Does the Clinical Pharmacogenetics Laboratory Do?

As part of “Personalized Medicine,” pharmacogenetics examines variations in how individuals respond to medications due to differences in their genetic makeup. Differences in genetic structures that play a role in drug metabolism or affect the mechanism of action can influence a drug’s efficacy and/or adverse effects in some individuals. With certain genetic tests currently in use, situations that may lead to unnecessary treatment or high risks of side effects can be identified in advance.

What Is a Pharmacogenetic Test?

Pharmacogenetic tests are genetic tests that analyze an individual’s genetic makeup to predict how drugs will affect their body and to aid in the development of personalized treatments. These tests aim to identify specific genetic variations associated with drug metabolism, mechanisms of action, and side effects. Pharmacogenetic tests can help determine the most effective and safest treatment for a patient and help minimize side effects. Today, two main methods are used in the treatment of diseases:

1. Trial-and-Error Method: The drug is administered until it demonstrates an effect.
2. Protocol Approach: A diagnosis is made first. Drugs are administered according to the decision tree in the protocol.

There are two primary clinical applications of pharmacogenetic studies:

1. Assessment of Drug Response: It determines which patients will respond well to specific medications and which will not. This allows for the personalization of effective treatment regimens.
2. Prevention of Side Effects: Patients who may experience side effects from medications are identified in advance. This reduces the risk of side effects and enhances medication safety.

Laboratory tests are used to achieve these goals. Therapeutic drug monitoring (TDM) is used to track the effects of medications and determine genetic profiles. Additionally, phenotyping is performed using a “probe drug.” The field of pharmacogenetics predicts drug responses, interactions, and side effects based on patients’ genetic makeup and contributes to the development of personalized treatment approaches.

In our country, therapeutic drug monitoring is limited and performed using nonspecific methods. However, pharmacogenetics aims to increase the efficacy and safety of drug therapy by advancing the concept of personalized treatment. Advances in this field can contribute to better disease management and improved treatment response.

What Are Pharmacogenetic Tests Used For?

Pharmacogenetic tests are genetic tests that analyze an individual’s genetic makeup to predict how drugs will affect their body and to help develop personalized treatments. These tests are used for the following purposes:

Predicting Drug Response: Pharmacogenetic tests help determine whether a drug is suitable for an individual’s genetic profile. Drugs can work differently in each person, and these tests can help predict how a drug will respond to a person’s condition.

Adjusting Drug Dosage: Genetic differences among individuals can affect how drugs are metabolized. Pharmacogenetic tests can be critical in determining the appropriate dose of a drug. Adjusting the dosage to match a person’s genetic profile can increase treatment effectiveness and reduce side effects.

Reducing Side Effects: Side effects of certain medications may arise due to genetic variations among individuals. Pharmacogenetic tests can predict which side effects an individual is at risk for and help make treatment safer.

Investigating Treatment Resistance: Some patients may be resistant to certain medications. Pharmacogenetic testing can help identify the cause of this resistance and suggest alternative treatment options.

Assessment of Drug Interactions: Pharmacogenetic testing can help evaluate how multiple medications used simultaneously interact within the body. This is important for the safety and efficacy of drug combinations.

Drug Development and Drug Selection: Pharmacogenetic studies are used in drug development processes and to determine whether new drugs are suitable for patients with specific genetic profiles. This can help in designing more targeted treatments.

Brochure: Personalized Medicine

Click here to download the booklet “Personalized Medicine: Clinical Pharmacogenetics, Genetics-Based Treatment Options.”

TDM MOLECULE LIST
S.No	Active Ingredient	Drug Half-Life (t 1/2) (Hours–Days)	Therapeutic Range	Alarm Level	Recommended Drug Administration Order for TDM
1.	Alprazolam	12–15 hours	20–40	100 ng/ml	3
2.	Acamprosate	3–33 hours	250–700	1000 ng/mL	3
3.	Amisulpiride	12–20 hours	100–320	640 ng/mL	1
4.	Amitriptyline + Nortriptyline	10–28 hours + 18–44 hours	80–200	300 ng/mL	1
5.	Aripiprazole	60–80 hours	100–350	1,000 ng/mL	2
6.	Asenapine	13–39 hours	1–5	10 ng/mL	4
7.	Atomoxetine	2–5 hours	200–1,000	2,000 ng/mL	3
8.	Bupropion + Hydroxybupropion	1–15 hours + 17–47 hours	850–1,500	2,000 ng/mL	2
9.	Buspirone	1–5 hours	1–4	30 ng/mL	3
10.	Carbamazepine	10–20 hours	4–12	20 µg/mL	1
11.	Carbamazepine 10-11 Epoxide	-	0.4–4	4 µg/mL	-
12.	Chlorpromazine	15–30 hours	30–300	600 ng/mL	2
13.	Citalopram	38–48 hours	50–110	220 ng/mL	1
14.	Clomipramine	16–60 hours	230–450	450 ng/mL	1
15.	Clonazepam	19–40 hours	4–80	100 ng/mL	3
16.	Clozapine + Norclozapine	12–16 hours	350–600	1,000 ng/mL	1
17.	DDTC_ME (Disulfiram Diethylthiomethylcarbamate-methyl ester)	6–9 hours	270–310	500 ng/mL	3
18.	Diazepam	24–48 hours	100–2,500	3,000 ng/mL	4
19.	Donepezil	70–80 hours	50–75	75 ng/mL	2
20.	Duloxetine	9–19 hours	30–120	240 ng/mL	2
21.	Escitalopram	27–32 hours	15–80	160 ng/mL	2
22.	Fluoxetine	4–6 days	120–500	1,000 ng/mL	3
23.	Flupenthixol	20–40 hours	0.5–5	15 ng/mL	2
24.	Fluphenazine	16 hours	1–10	15 ng/mL	1
25.	Fluvoxamine	21–43 hours	60–230	500 ng/mL	2
26.	Gabapentin	5–7 hours	2–20	25 µg/mL	3
27.	Haloperidol	12–36 hours	1–10	15 ng/mL	1
28.	Imipramine + Desimipramine	11–25 hours + 15–18 hours	175–300	300 ng/mL	1
29.	Lacosamide	10–15 hours	1–10	20 µg/mL	3
30.	Lamotrigine	14–104 hours	1–15	20 µg/mL	2
31.	Levetiracetam	6–8 hours	20–40	50 µg/mL	4
32.	Lorazepam	12–16 hours	30–100	300 ng/mL	4
33.	Maprotiline	20–58 hours	75–130	220 ng/mL	2
34.	Memantine	60–100 hours	90–150	300 ng/mL	3
35.	Metformin	6.2 hours	1–2	5 µg/mL	-
36.	Methylphenidate	2 hours	6–26	50 ng/mL	3
37.	Mianserin	14–33 hours	15–70	140 ng/mL	3
38.	Milnacipran	5–8 hours	100–150	300 ng/mL	2
39.	Mirtazapine	20–40 hours	30–80	160 ng/mL	2
40.	Moclobemide	2–7 hours	300–1,000	2,000 ng/mL	3
41.	Modafinil	10–12 hours	100–1,700	3,400 ng/mL	3
42.	Naltrexone + 6β-naltrexol	2–5 hours + 7–13 hours	25–100	200 ng/mL	2
43.	Olanzapine	30–60 hours	20–80	100 ng/mL	1
44.	Opipramol	11 hours	50–500	1000 ng/mL	3
45.	Oxcarbazepine (Oxcarbazepine 10-hydroxycarbazepine)	10–20 hours	10–35	40 µg/mL	2
46.	Paliperidone (9-hydroxyrisperidone)	17–23 hours	20–60	120 ng/mL	2
47.	Paroxetine	12–44 hours	20–65	120 ng/mL	3
48.	Pimozide	23–43 hours	15–20	20 ng/mL	3
49.	Pramipexole	8–12 hours	0.4–1.2	15 ng/mL	3
50.	Pregabalin	5–7 hours	2–5	10 µg/mL	3
51.	Quetiapine	6–13 hours	100–500	1,000 ng/mL	2
52.	Reboxetine	13–30 hours	60–350	700 ng/mL	3
53.	Risperidone + 9-hydroxy-risperidone	2–4 hours + 17–23 hours	20–60	120 ng/mL	2
54.	Rivastigmine	1–2 hours	8–20	40 ng/mL	3
55.	Sertindole	55–90 hours	50–100	200 ng/mL	2
56.	Sertraline	22–36 hours	10–150	300 ng/mL	2
57.	Sulpiride	8–14 hours	200–1,000	1,000 ng/mL	2
58.	Tianeptine	2.5–3 hours	30–80	160 ng/mL	3
59.	Topiramate	19–23 hours	2–10	16 µg/mL	3
60.	Trazodone	4–11 hours	700–1,000	1,200 ng/mL	2
61.	Trifluoperazine	-	1–2.3	-	-
62.	Venlafaxine + O-desmethylvenlafaxine (ODV)	14–18 hours + 10–17 hours	100–400	800 ng/mL	2
63.	Valproic acid	17–30 hours	50–100	120 µg/mL	1
64.	Vortioxetine	57–66 hours	10–40	80 ng/mL	2
65.	Ziprasidone	4–8 hours	50–200	400 ng/mL	2
66.	Zolpidem	1–4 hours	80–160	320 ng/mL	4
67.	Zuclopenthixol	15–25 hours	4–50	100 ng/mL	3