The Impact of CYP2D6 Polymorphism on Tramadol Pharmacodynamics

The Outcome of CYP2D6 Polymorphism on Tramadol Analgesia in Postpartum Patients in Erbil

CYP2D6 is an enzyme involved in the hepatic metabolism of many clinically important drugs: antiarrhythmics, antidepressants, antipsychotics, β-blockers, and analgesics such as tramadol and codeine. CYP2D6 is highly polymorphic and significant interindividual variability has been observed worldwide. This study aims to investigate the distribution of CYP2D6 polymorphisms among post-cesarean female patients in Erbil city, Iraq. The findings of this study may indicate the presence of CYP2D6 gene variants among the Kurdish female population in Erbil, which could contribute to tramadol analgesic failure or exaggerated adverse effects. This study could also serve as a foundation for further pharmacogenetic research, individualizing treatments and targeting a larger sample size in the future.

Study Overview

• Status: Active, not recruiting
• Conditions: CYP2D6 Polymorphism; Post-cesarean Pain; Tramadol Resistance
• Intervention / Treatment: Drug: Trodon® Hemofarm

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Iraq
  • Erbil, Iraq, 40/0112
    • Hawler Medical University/ College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pregnant patients who were indicated for elective cesarean section surgery at public hospital (Maternity Teaching hospital) located in Erbil city, Iraq were enrolled.

Description

Inclusion Criteria:

• Female patients aged between 18-56 years old
• Patients who undergo cesarean section surgery
• Patients receive tramadol drug for postpartum pain management

Exclusion Criteria:

• Patients with any history of severe renal, liver, respiratory diseases and/or seizures
• Patients with history of psychiatric disorders or unable to provide consent
• Patients with complicated surgeries or neonatal distress or unable to perform the clinical assessment of pain
• Patients with history of consumption of chronic alcohol or opioid or drug abuse
• Patients with history of known allergy to tramadol

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

post-cesarean patients; All of these patients were planned to undergo elective cesarean surgery and receive postpartum management for twenty-four hours at the Erbil Maternity and Childbirth Hospital. Consent was taken from each patient prior to the enrollment into the study. Their age ranged between 21-42 years. Patients received one dose of tramadol drug (100mg/2ml of Trodon® Hemofarm) intravenously for management of postpartum pain after gaining back their pain sensation.

Drug: Trodon® Hemofarm; Consent was taken from each patient prior to the enrollment into the study during the first interview and 2 ml of blood was withdrawal for the CYP2D6 genotyping. After the cesarean section surgery, each patient received one dose of 100mg/2ml Trodon® Hemofarm for treating the postpartum pain and the patients were monitored for 24 hours. Follow-up was performed for each enrolled patient in which the VAS score, blood pressure, heart rate, oxygen saturation and any new effects after 1 hour, 6 hours of tramadol administration were recorded. In addition, after 24 hours evaluations for nocturnal pain, dietary state and bowel movement were performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual analog scale (10 cm)	Visual analog scale is used for measuring pain intensity on a scale of 0 to 10, in which a score on the line is marked by each patient ranging from "no pain" to "worst pain". The pain intensity increases as the score on the scale goes up.	after 1 hour and 6 hours of receiving single dose of tramadol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure (mm of Hg)	Blood pressure was measured by automatic blood pressure monitor (mm of Hg) after 1 hour and 6 hours of IV tramadol administration to detect any change in the blood pressure of each patient.	after 1 hour and 6 hours of receiving single dose of tramadol
Heart rate (beats per minute)	Pulse was recorded by pulse oximetry (beats per minute) after 1 hour and 6 hours of IV tramadol administration to detect any change in the heart rate of each patient.	after 1 hour and 6 hours of receiving single dose of tramadol
Oxygen saturation (SPO2%)	Oximetry was used (SPO2 %) for evaluating the oxygen saturation of each patient.	after 1 hour and 6 hours of receiving single dose of tramadol
Nocturnal pain	Evaluation of nocturnal pain was performed for each patient by a questionnaire after 24 hours to determine pain at night and whether it has impacted on the sleeping quality of the patient.	after 24 hours of receiving single dose of tramadol
Dietary state	Evaluation of dietary state was performed for each patient, in which the patient was asked after 24 hours to determine whether they have taken anything within the last 24 hours and if yes did they take liquid and/or solid food.	after 24 hours of receiving single dose of tramadol
Adverse effects	A questionnaire was presented to each patient for recording any newly appearing effects that are noticed by the patient after 1 hour and 6 hours of receiving single dose of tramadol drug intravenously. In addition, the patient was asked after 24 hours whether they had had bowel movement within the last 24 hours (whether the patient was constipated).	after 1 hour and 6 hours of receiving single dose of tramadol for recording any adverse effects, and after 24 hours of receiving single dose of tramadol for evaluation of the bowel movement (whether the patient was constipated).

Collaborators and Investigators

• Sponsor: Elweyia Maternity Teaching Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2024
• Primary Completion (Actual): December 20, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: January 28, 2025
• First Submitted That Met QC Criteria: February 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: ElweyiaMTH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No