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Methadone Dose (methadone + dose)

Distribution by Scientific Domains

Medical Sciences	66%

Selected Abstracts

Methadone dose and post-mortem blood concentration

DRUG AND ALCOHOL REVIEW, Issue 4 2002
Dr. JOHN R. M. CAPLEHORN
Abstract The relationship of methadone dose with post-mortem blood concentration was investigated using data collected from 1994 coronial cases in the Australian state of New South Wales. Data on 31 subjects were summarized using linear regression. The weight-adjusted methadone dose, gender, methadone maintenance treatment status and its interaction with adjusted-dose were all significant predictors of post-mortem blood methadone concentration. Data on the death of a young man from the toxic effects of three daily doses of 30mg methadone are used to give an example of a pair of observed (0.74 mg/l) and predicted (0.48 mg/l) post-mortem blood concentrations. The estimated post-mortem blood concentration for male maintenance patients is at least twice the trough plasma levels estimated from previously published studies of living maintenance patients. The estimated post-mortem blood concentration for female maintenance patients is at least three times the estimated trough level of living subjects. We conclude that post-mortem methadone redistribution is probably the principal cause of the observed differences between males and females in post-mortem blood concentrations and the differences between estimated concentrations for living and deceased subjects. [source]

Methadone doses of 100 mg or greater are more effective than lower doses at suppressing heroin self-administration in opioid-dependent volunteers

ADDICTION, Issue 10 2005
Eric C. Donny
ABSTRACT Aims Methadone maintenance has been an effective pharmacotherapy for the treatment of heroin dependence for nearly four decades. Recent clinical research suggests that methadone doses larger than those used in most clinics are more effective at suppressing illicit heroin use. This greater efficacy may result from greater cross-tolerance to the reinforcing effects of heroin. Design The purpose of this double-blind, within-subject study was to examine the relationship between methadone maintenance dose and the reinforcing effects of heroin. Setting Participants were stabilized on 50, 100 and 150 mg methadone (ascending order) during separate outpatient periods before being admitted to an inpatient research unit for testing at each maintenance dose. Participants Five opiate-dependent volunteers completed the study. Measurements During each 4-week inpatient testing period, participants sampled three doses of heroin (0, 10, or 20 mg; random order; one dose per week) and were subsequently allowed seven opportunities to choose between another injection of that week's heroin dose and varying amounts of money ($2,38). Findings The number of heroin injections chosen decreased as methadone dose was increased. Larger alternative monetary reinforcers were required to suppress heroin self-administration during maintenance on 50 compared to 100 or 150 mg methadone. Larger methadone doses also completely blocked the subjective effects of heroin and produced greater withdrawal suppression during the outpatient periods. Conclusions These results support other clinical and laboratory-based research indicating that persistent heroin use may be reduced by providing larger methadone maintenance doses that produce more effective cross-tolerance to heroin. [source]

Methadone dose and post-mortem blood concentration

Methadone doses of 100 mg or greater are more effective than lower doses at suppressing heroin self-administration in opioid-dependent volunteers

CLINICAL STUDY: Effect of saquinavir/ritonavir (1000/100 mg bid) on the pharmacokinetics of methadone in opiate-dependent HIV-negative patients on stable methadone maintenance therapy

ADDICTION BIOLOGY, Issue 3 2009
Candice Jamois
ABSTRACT This study was performed to determine the effect of two protease inhibitors, saquinavir (SQV, oral 1000 mg bid) boosted by ritonavir (RTV, oral 100 mg bid), on pharmacokinetics (PK) of methadone in opiate-dependent HIV-negative patients on stable methadone maintenance therapy. This was a two-center, open-label, one-sequence cross-over, multiple-dose study in 13 HIV-negative patients who were on stable methadone therapy (oral, 60,120 mg qd). All patients continued methadone treatment on days 2,15. All patients received SQV/RTV in combination with methadone from days 2,15. PK of methadone was assessed on day 1 (alone) and on day 15 when methadone treatment was combined with SQV/RTV at steady state. Twelve patients completed the study. Median age, body weight and height were 50 years (range: 24,54 years), 80 kg (range: 57,97 kg) and 174 cm (range: 163,189 cm), respectively. All patients were Caucasian, and 11 were smokers. Median methadone dose was 85 mg qd. Geometric mean area under curve of the plasma concentration-time curve over 24 hour dosing interval (AUC0,24 hour) ratio of methadone with and without SQV/RTV was 0.81% (90% confidence interval: 71,91%). There was no significant plasma protein-binding displacement of methadone by SQV/RTV. The combination of SQV/RTV and methadone was well tolerated. There were no clinically significant adverse events or significant changes in laboratory parameters, electrocardiograms or vital signs. The 19% decrease in R-methadone AUC0,24 hour in the presence of SQV/RTV was not clinically relevant. There appears to be no need for methadone dose adjustment when methadone (60,120 mg qd) and SQV/RTV (1000/100 mg bid) are coadministered. [source]

Experience of Methadone Therapy in 100 Consecutive Chronic Pain Patients in a Multidisciplinary Pain Center

PAIN MEDICINE, Issue 7 2008
FRCPC, Philip Peng MBBS
ABSTRACT Objective., The objective of the study was to describe the experience of methadone use in 100 consecutive chronic pain patients managed in a single multidisciplinary center. Design., A chart review of chronic pain patients on methadone therapy initiated at the Wasser Pain Management Center from January 2001 to June 2004. Setting, Patients, and Intervention., Outpatients receiving methadone for chronic pain management in a tertiary multidisciplinary pain center. Outcome Measure., Effects on pain relief and function, conversion ratio from other opioids, side effects, and disposition were reviewed. Results., Charts of 100 methadone patients (age 45 ± 11 years old; M/F: 3/7; duration of pain 129 ± 110 months) managed by five physicians and one nurse were reviewed. The main reason for the initiation of methadone therapy was opioid rotation (72%). The average oral morphine equivalent dose was 77 mg/day before methadone therapy, and the methadone dose after initial stabilization was 42 mg with no consistent conversion ratio observed. The mean duration of methadone therapy was 11 months. Most of the patients (91%) were taking concomitant adjuvant analgesics or psychotropic agents, mostly antidepressants and anticonvulsants. The average Numeric Verbal Rating Score before and after methadone treatment was 7.2 ± 1.7 and 5.2 ± 2.5 (P < 0.0001). Thirty-five patients discontinued their methadone treatment mainly because of side effects, ineffectiveness, or both. Conclusion., From our experience, methadone is an effective alternative to conventional opioids for chronic pain management when used by experienced clinicians in a setting that allows for close monitoring and careful dose initiation and adjustment. [source]

Perinatal risk factors for the neonatal abstinence syndrome in infants born to women on methadone maintenance therapy

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2010
Anthony J.W. LIU
Background:, Neonatal abstinence syndrome (NAS) occurs in more than 50% of infants exposed to intrauterine opiates. Maternal opiate dosing has been investigated with conflicting results. Aims:, The aims of this study were to correlate maternal methadone dose and other risk factors with the development of NAS requiring pharmacological treatment by using easily accessible clinical parameters. Methods:, Retrospective medical record review of data from 228 opioid dependent pregnant women who delivered 232 live-born infants. Logistic regression analysis was performed on maternal, perinatal and neonatal parameters to identify risk factors for NAS requiring treatment. A prediction model was developed and validated on a separate independent cohort of 188 infants. Results:, Of the 232 infants, 172 (74%) infants were treated for NAS. The risk of withdrawal increased by 17% per 5 mg increment of the last maternal methadone dose. The risk was lower for younger gestational ages and for those delivered by Caesarean section compared to those delivered by normal vaginal delivery. Through predictive modeling, gestational age, mode of delivery and last methadone dose were established as risk factors for withdrawal. The model was validated by other statistical measures and its diagnostic performance confirmed on the separate independent cohort. Conclusions:, Our data suggests that timing and mode of delivery as well as last maternal methadone dose are significant risk factors for the development of NAS requiring treatment. Based on these clinical parameters, risk stratification for perinatal management of pregnancies associated with opioid dependency and risk prediction for the neonate might now be possible. [source]

Pharmacokinetic interaction of nelfinavir and methadone in intravenous drug users

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2006
Poe-Hirr Hsyu
Abstract The effect of nelfinavir 1250 mg twice daily (b.i.d.) on the pharmacokinetics of methadone was determined in 14 HIV-negative methadone users. Design: The methadone dose (20,140 mg/day) was stabilized and fixed for at least 1 month before nelfinavir (1250 mg b.i.d. for 8 days) was added to the regimen. The concentrations of methadone enantiomers were measured before and during nelfinavir treatment, and the concentrations of nelfinavir and its active metabolite, AG1402, were measured during nelfinavir treatment. Adverse events and withdrawal/intoxication symptoms were monitored throughout the study. Results: Nelfinavir reduced the area under the concentration-time curve of R-methadone, and S-methadone by 43% and 51%, respectively. Nelfinavir and AG1402 concentrations were within the normal range of historical data, and no subject experienced withdrawal symptoms during the study or required dose adjustment during or after the study. Conclusions: Although nelfinavir reduced the plasma concentrations of both R- and S-methadone, it seems to have no impact on the maintenance dose of methadone. A routine reduction of methadone dose is not recommended when coadministered with nelfinavir. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Opioid switching from transdermal fentanyl to oral methadone in patients with cancer pain

CANCER, Issue 12 2004
Miguel Angel Benítez-Rosario M.D., Ph.D.
Abstract BACKGROUND Patients with cancer often are rotated from other opioids to methadone to improve the balance between analgesia and side effects. To the authors' knowledge, no clear guidelines currently exist for the safe and effective rotation from transdermal fentanyl to methadone. METHODS The authors evaluated a protocol for switching opioid from transdermal fentanyl to oral methadone in 17 patients with cancer. Reasons for switching were uncontrolled pain (41.1% of patients) and neurotoxic side effects (58.9% of patients). Methadone was initiated 8,24 hours after fentanyl withdrawal, depending on the patient's previous opioid doses (from < 100 ,g per hour to > 300 ,g per hour). The starting methadone dose was calculated according to a 2-step conversion between transdermal fentanyl:oral morphine (1:100 ratio) and oral morphine:oral methadone (5:1 ratio or 10:1 ratio). The correlation between previous fentanyl dose and the final methadone dose or the fentanyl:methadone dose ratio was assessed by means of Pearson and Spearman correlation coefficients (r), respectively. A Friedman test was used to compare pain intensity before and after the switch and the use of daily rescue doses. RESULTS Opioid rotation was fully or partially effective in 80% and 20%, respectively, of patients with somatic pain. Neuropathic pain was not affected by opioid switching. Delirium and myoclonus were reverted in 80% and 100% of patients, respectively, after opioid switching. A positive linear correlation was obtained between the fentanyl and methadone doses (Pearson r, 0.851). Previous fentanyl doses were not correlated with the final fentanyl:methadone dose ratios (Spearman r, , 0.327). CONCLUSIONS The protocol studied provided a safe approach for switching from transdermal fentanyl to oral methadone, improving the balance between analgesia and side effects in patients with cancer. Cancer 2004. © 2004 American Cancer Society. [source]

Patients' help-seeking behaviours for health problems associated with methadone and buprenorphine treatment

DRUG AND ALCOHOL REVIEW, Issue 4 2008
ADAM R. WINSTOCK
Abstract Introduction and Aims. Clients in opioid substitution therapy often have considerable unmet health-care needs. The current study aimed to explore health problems related to opioid substitution therapy among clients on methadone and buprenorphine treatment. Design and Methods. A self-complete, cross-sectional survey conducted among 508 patients receiving methadone and buprenorphine treatment at community pharmacies in New South Wales (NSW), Australia. Results. The most common problems for which participants had ever sought help were dental (29.9%), constipation (25.0%) and headache (24.0%). The most common problems for which participants would currently like help were dental (41.1%), sweating (26.4%) and reduced sexual enjoyment (24.2%). There were no significant differences between those currently on methadone and those currently on buprenorphine for any of the health problems explored, nor differences for gender or treatment duration. Participants on methadone doses 100 mg or above were significantly more likely to want help currently for sedation. Discussion and Conclusions. The considerable unmet health care needs among participants in this study suggest that treatment providers should consider improving the detection and response to common health problems related to opioid substitution therapy. [source]

Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment study

ADDICTION, Issue 6 2009
Katinka Anchersen
ABSTRACT Aims To determine the prevalence of corrected QT interval (QTc) prolongation among patients in opioid maintenance treatment (OMT) and to investigate mortality potentially attributable to QTc prolongation in the Norwegian OMT programme. Participants and setting Two hundred OMT patients in Oslo were recruited to the QTc assessment study between October 2006 and August 2007. The Norwegian register of all patients receiving OMT in Norway (January 1997,December 2003) and the national death certificate register were used to assess mortality. Mortality records were examined for the 90 deaths that had occurred among 2382 patients with 6450 total years in OMT. Design and measures The QTc interval was assessed by electrocardiography (ECG). All ECGs were examined by the same cardiologist, who was blind to patient history and medication. Mortality was calculated by cross-matching the OMT register and the national death certificate register: deaths that were possibly attributable to QTc prolongation were divided by the number of patient-years in OMT. Findings In the QTc assessment sample (n = 200), 173 patients (86.5%) received methadone and 27 (13.5%) received buprenorphine. In the methadone group, 4.6% (n = 8) had a QTc above 500 milliseconds; 15% (n = 26) had a QTc interval above 470 milliseconds; and 28.9% (n = 50) had a QTc above 450 milliseconds. All patients receiving buprenorphine (n = 27) had QTc results <450 milliseconds. A positive dose-dependent association was identified between QTc length and dose of methadone, and all patients with a QTc above 500 milliseconds were taking methadone doses of 120 mg or more. OMT patient mortality, where QTc prolongation could not be excluded as the cause of death, was 0.06/100 patient-years. Only one death among 3850 OMT initiations occurred within the first month of treatment. Conclusion Of the methadone patients, 4.6% had QTc intervals above 500 milliseconds. The maximum mortality attributable to QTc prolongation was low: 0.06 per 100 patient-years. [source]