Methadone Pharmacokinetics in End-stage Renal Disease

NCT06056245 | Recruiting

• 1 other identifier: 230125010
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to describe the influence of renal function on the pharmacokinetics of methadone used through an intravenous patient-controlled analgesia (IV-PCA) pump for the management of acute postoperative pain. After surgery the participants will use an IV-PCA of methadone and blood samples will be withdrawn to measure the plasmatic levels of it. The main question the study aims to answer is: • Is the pharmacokinetic of methadone used in an IV-PCA pump impaired in patients with chronic kidney disease?

Conditions

Chronic Kidney Diseases; Post Operative Pain; Pain, Acute

Keywords

Methadone; Patient Controlled Anesthesia; Chronic Kidney Diseases; Post Operative Pain

Outcome Measures

Primary Outcomes (1)

• Plasma concentration

  Blood samples will be taken, collected in heparin tubes, and centrifuged. The extracted serum will be placed in cryotubes that will be stored at -80 °C until analysis. Methadone samples will be analyzed using a high performance liquid chromatography (HPLC) spectrofluorometric method. Lower limits of quantification (LLOQ) will be determined and samples below the LLOQ will not be included in the analysis.

  5, 15, 30, 60 minutes and 2, 4, 6, 9, 12, 24, 36 and 72 hours after the intraoperative bolus of methadone

Secondary Outcomes (6)

• Total use of methadone

  2, 4, 6, 9, 12, 24, 36 and 48 hours after the intraoperative bolus of methadone

• Post-operative Pain

  2, 4, 6, 9, 12, 24, 36 and 48 hours after the intraoperative bolus of methadone

• Nausea or vomiting

  2, 4, 6, 9, 12, 24, 36 and 48 hours after the intraoperative bolus of methadone

• Respiratory depression

  2, 4, 6, 9, 12, 24, 36 and 48 hours after the intraoperative bolus of methadone

• Hypoxemia

  2, 4, 6, 9, 12, 24, 36 and 48 hours after the intraoperative bolus of methadone

Study Arms (1)

Study group

Patients with chronic kidney disease (CKD) over 18 years old undergoing surgery using general anesthesia with subsequent use of intravenous patient-controlled analgesia (IV-PCA) of methadone.

Procedure: Preoperative step; Drug: Intraoperative; Drug: Post-operative

Interventions

Preoperative step PROCEDURE

* Explanation of the surgery and use of the IV-PCA pump. * Signed informed consent.

Study group

Intraoperative DRUG

Bolus of methadone 0.1mg/kg based on ideal body weight (up to a maximum dose of 20 mg), at the beginning of surgery.

Also known as: Methadone administration during surgery

Study group

Post-operative DRUG

Installation of IV-PCA of methadone. Program to be used with no background infusion, boluses of 1 mg, and the intervals between boluses of 8 minutes.

Also known as: Methadone boluses administered by IV-PCA pump

Study group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients over 18 years old with a diagnosis of chronic kidney disease undergoing surgery requiring general anesthesia whose hospital stay is a minimum of 48 hours.

You may qualify if:

• Patients with chronic kidney disease (CrCl 15-60 ml/min)
• Patients over 18 years old undergoing surgery requiring general anesthesia with subsequent use of intravenous methadone patient-controlled analgesia
• Hospital stay ≥ 48 hours
• Body mass index 18-35 kg/m2

You may not qualify if:

• History of liver disease
• Need for dialysis (hemo or peritoneal dialysis)
• Use of home oxygen therapy
• American Society of Anesthesiologists (ASA) physical status IV-V
• Pregnancy
• Chronic opioid use
• Methadone allergy
• Prolonged QT interval
• Use of antiarrhythmics that prolong the QT interval
• Inability to understand the proper use of PCA

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Pontificia Universidad Católica de Chile

Santiago, 7550000, Chile

RECRUITING

Related Publications (10)

• Kreek MJ, Schecter AJ, Gutjahr CL, Hecht M. Methadone use in patients with chronic renal disease. Drug Alcohol Depend. 1980 Mar;5(3):197-205. doi: 10.1016/0376-8716(80)90180-5.

  PMID: 6986247 BACKGROUND

• Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. doi: 10.1097/00000542-198212000-00005. No abstract available.

  PMID: 6128949 BACKGROUND

• Inturrisi CE, Colburn WA, Kaiko RF, Houde RW, Foley KM. Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain. Clin Pharmacol Ther. 1987 Apr;41(4):392-401. doi: 10.1038/clpt.1987.47.

  PMID: 3829576 BACKGROUND

• Sharma A, Tallchief D, Blood J, Kim T, London A, Kharasch ED. Perioperative pharmacokinetics of methadone in adolescents. Anesthesiology. 2011 Dec;115(6):1153-61. doi: 10.1097/ALN.0b013e318238fec5.

  PMID: 22037641 BACKGROUND

• Davies G, Kingswood C, Street M. Pharmacokinetics of opioids in renal dysfunction. Clin Pharmacokinet. 1996 Dec;31(6):410-22. doi: 10.2165/00003088-199631060-00002.

  PMID: 8968655 BACKGROUND

• Stemland CJ, Witte J, Colquhoun DA, Durieux ME, Langman LJ, Balireddy R, Thammishetti S, Abel MF, Anderson BJ. The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion. Paediatr Anaesth. 2013 Jan;23(1):51-7. doi: 10.1111/pan.12021. Epub 2012 Sep 14.

  PMID: 22978825 BACKGROUND

• Yin OQ, Merante D, Truitt K, Miller R. Population pharmacokinetic modeling and simulation for assessing renal impairment effect on the pharmacokinetics of mirogabalin. J Clin Pharmacol. 2016 Feb;56(2):203-12. doi: 10.1002/jcph.584. Epub 2015 Sep 2.

  PMID: 26138993 BACKGROUND

• Ji XW, Ji SM, He XR, Zhu X, Chen R, Lu W. Influences of renal function descriptors on population pharmacokinetic modeling of vancomycin in Chinese adult patients. Acta Pharmacol Sin. 2018 Feb;39(2):286-293. doi: 10.1038/aps.2017.57. Epub 2017 Aug 24.

  PMID: 28836582 BACKGROUND

• Murphy GS, Szokol JW. Intraoperative Methadone in Surgical Patients: A Review of Clinical Investigations. Anesthesiology. 2019 Sep;131(3):678-692. doi: 10.1097/ALN.0000000000002755. No abstract available.

  PMID: 31094758 BACKGROUND

• Kreutzwiser D, Tawfic QA. Methadone for Pain Management: A Pharmacotherapeutic Review. CNS Drugs. 2020 Aug;34(8):827-839. doi: 10.1007/s40263-020-00743-3.

  PMID: 32564328 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Pain, Postoperative; Acute Pain

Interventions

Postoperative Period

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Perioperative Period; Surgical Procedures, Operative; Patient Care; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Eduardo Vega, MD

  Pontificia Universidad Catolica de Chile

  STUDY DIRECTOR

Central Study Contacts

Eduardo Vega, MD

CONTACT

223543270; eavega@uc.cl

Victor Contreras, MSN

CONTACT

223549217; vecontre@uc.cl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2023
• First Posted: September 28, 2023
• Study Start: April 5, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: May 10, 2024

Record last verified: 2024-05

Locations

CL (1)