Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of methadone in a sample of Iranian (Mazandarani) opiate users undergoing methadone maintenance treatment

Mohammad-Reza Shiran; Hosseinzadeh Rasa; Abolhassan Hamidikenari; Mehran Zarghami; Nargess Lamsehchi; Mohammad-Reza Rafati

IJ Psychiatry and Behavioral Sciences

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Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of methadone in a sample of Iranian (Mazandarani) opiate users undergoing methadone maintenance treatment

Author(s):

Mohammad-Reza Shiran^1,*,

Hosseinzadeh Rasa ¹,

Abolhassan Hamidikenari¹,

Mehran Zarghami¹,

Nargess Lamsehchi¹,

Mohammad-Reza Rafati²

1Psychiatry and Behavioral Sciences Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

2Department of Pharmacotherapy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

IJ Psychiatry and Behavioral Sciences:Vol. 5, issue 2; 53-61

Published online:Dec 31, 2011

Article type:Research Article

Received:Apr 20, 2011

Accepted:Jul 04, 2011

How to Cite:Shiran M, Rasa H, Hamidikenari A, Zarghami M, Lamsehchi N, et al. Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of methadone in a sample of Iranian (Mazandarani) opiate users undergoing methadone maintenance treatment.Iran J Psychiatry Behav Sci.2011;5(2):53-61.

Abstract

Objective: To investigate the pharmacokinetics (PK) and PK- pharmacodynamic (PD) relationship of methadone in a cohort of outpatients undergoing methadone maintenance treatment (MMT).

Methods: Sixty male patients undergoing MMT with a mean ±SD methadone daily dosage of 58 ± 34 mg were enrolled in this study. A 5-ml blood sample was collected before the daily intake of methadone. As a PD measure, the Subjective Opioid Withdrawal Scale (SOWS) form was completed immediately after obtaining the blood sample. Blood samples were taken and the forms were completed 4-5 times more (up to 24 hr) after the daily intake of methadone. Plasma methadone was analyzed using HPLC. Population PK/PD analysis was performed using population pharmacokinetics modeling software P-Pharm.

Results: Significant decreases (p< 0.05) were observed in the SOWS scores during 10 hours after methadone intake. The SOWS had returned to baseline by 24 hr after using methaodone (p= 0.98). A considerable interindividual variability in the CL/F (16 fold), EC50 (3 fold) and Emax (6 fold) for methadone was observed.

Conclusion: Withdrawal symptoms were significantly improved in MMT patients after taking methadone and the PD measure was substantially affected by fluctuations in plasma methadone concentration. However, The SOWS had returned to baseline by 24 hr after using mathadone. Thus, a once daily dosing of methadone may not be suitable for those MMT patients who experience a significant withdrawal disturbance in the latter part of the interdose interval. This may increase the perceived severity of withdrawal and induce a craving for additional opioids.

Declaration of Interest: None.

Citation: Shiran MR, Hosseinzadeh R, Hamidikenari A, Zarghami M, Lamsehchi N, Rafati MR. Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of methadone in a sample of Iranian (Mazandarani) opiate users undergoing methadone maintenance treatment. Iran J Psychiatry Behav Sci 2011; 5(2): 53-61.

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Search Relations

Author(s):

Mohammad-Reza Shiran:[PubMed][Scholar]
Hosseinzadeh Rasa :[PubMed][Scholar]
Abolhassan Hamidikenari:[PubMed][Scholar]
Mehran Zarghami:[PubMed][Scholar]
Nargess Lamsehchi:[PubMed][Scholar]
Mohammad-Reza Rafati:[PubMed][Scholar]