Abstract
The purpose of this study was to investigate the blood levels of methadone in participants receiving methadone for the treatment of opioid dependence. After stabilization on methadone for four weeks, blood samples from 95 participants were collected between treatment weeks 4 and 12, before and after receiving doses of methadone, and its blood levels were measured. A multiple linear regression model was used to examine the association between methadone blood levels and the outcomes of methadone maintenance treatment (MMT). Outcome differences between participants who had high (≥2) or low (<2) peak-to-trough ratios were also compared using an independent sample t-test. The blood level of methadone was not correlated with the clinical outcome of MMT with the moderate range of doses given. However, the retention of patients who had a free peak-to-trough ratio >2 was significantly poorer than those whose ratio was <2. Thus, monitoring plasma methadone levels is unlikely to be effective for guiding dosing decisions in situations where compliance with MMT is already very high or when the methadone dose is no longer the dominant factor in determining the clinical outcome. However, monitoring plasma methadone levels is still helpful for guiding the dosage for patients with a rapid metabolism.
Similar content being viewed by others
References
Loimer N, Schmid R. The use of plasma levels to optimize methadone maintenance treatment. Drug Alcohol Depend 1992, 30(3): 241–246.
Mohamad N, Salehuddin RM, Ghazali B, Bakar NHA, Musa N, Ibrahim MA, et al. Plasma methadone level monitoring in methadone maintenance therapy: A personalised methadone therapy. In: Gowder S (Ed.), New insights into toxicity and drug testing. InTech; 2013, 236–237.
Nilsson MI, Grönbladh L, Widerlöv E, Änggård E. Pharmacokinetics of methadone in methadone maintenance treatment: characterization of therapeutic failures. Eur J Clin Pharmacol 1983, 25(4): 497–501.
Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone. Clin Pharmacokinet 2002, 41(14): 1153–1193.
Abramson FP. Methadone plasma protein binding: Alterations in cancer and displacement from α1‐acid glycoprotein. Clin Pharmacol Ther 1982, 32(5): 652–658.
Calvo R, Aguirre C, Troconiz I, López J, Garrido M. Alpha1-acid glycoprotein and serum protein binding of methadone in heroin addicts during withdrawal. Int J Clin Pharmacol Ther 2000, 38(1): 35–40.
Li Y, Kantelip J, Schieveen PG, Davani S. Interindividual variability of methadone response: impact of genetic polymorphism. Mol Diagn Ther 2008, 12(2): 109.
Sullivan SG, Wu Z, Rou K, Pang L, Luo W, Wang C, et al. Who uses methadone services in China? Monitoring the world’s largest methadone programme. Addiction 2015, 110(S1): 29–39.
Sullivan SG, Wu Z, Detels R, National methadone maintenance treatment working group. Time to first treatment interruption in the Chinese methadone maintenance treatment programme. Drug Alcohol Depend 2013, 133(2): 427–432.
Lin C, Detels R. A qualitative study exploring the reason for low dosage of methadone prescribed in the MMT clinics in China. Drug Alcohol Depend 2011, 117(1): 45–49.
Zhao M, Li X, Hao W, Wang Z, Zhang M, Xu D. A preliminary study of the reliability and validity of the Addiction Severity Index. J Chin Med Res 2004, 4(8): 679–680.(in Chinese)
Luo W, Wu Z, Wei X, Jia W, Zhang Q, Li L, et al. Chinese assimilation of the fifth edition of Addiction severity index scale and the evaluations on its applications in addiction status investigation. Chin J Drug Depend 2007, 16(5): 373–376.(in Chinese)
Dyer KR, Foster DJ, White JM, Somogyi AA, Menelaou A, Bochner F. Steady-state pharmacokinetics and pharmacodynamics in methadone maintenance patients: Comparison of those who do and do not experience withdrawal and concentration-effect relationships. Clin Pharmacol Ther 1999, 65(6): 685–694.
Sun A. Review and prospective for self-organized peer education. Anti-drug Social Work, 2010, 4(17): 5–8.(in Chinese)
Crettol S, Déglon JJ, Besson J, Croquette‐Krokkar M, Gothuey I, Hämmig R, et al. Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment. Clin Pharmacol Ther 2005, 78(6): 593–604.
Chitasombat P, Willenbring ML, Maddux T, Severeide N. Reliability of methadone plasma levels in methadone maintenance. Am J Addict 1995, 4(4): 351–355.
Drozdick J, Berghella V, Hill M, Kaltenbach K. Methadone trough levels in pregnancy. Am J Obstet Gynecol 2002, 187(5): 1184–1188.
Acknowledgements
This work was supported by the Research Project of Shanghai Municipal Health and Family Planning Commission, China (2013SY011 and 2014ZYJB0002), the National Natural Science Foundation of China (81271468), Doctoral Supervisor Funding from the Ministry of Education of China (20120073110089), and Research Funding from Shanghai Key Laboratory of Severe Mental illness, China (13dz2260500). We thank the patients and staff of the four Shanghai MMT clinics who participated in this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jiang, H., Hillhouse, M., Du, J. et al. Dose, Plasma Level, and Treatment Outcome Among Methadone Patients in Shanghai, China. Neurosci. Bull. 32, 538–544 (2016). https://doi.org/10.1007/s12264-016-0059-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12264-016-0059-0