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Can saliva replace plasma for the monitoring of methadone?

Abstract：

:The aims of this study were to determine the relationship between saliva and plasma methadone concentrations and the influence of variability in saliva pH. Saliva and plasma samples were taken before the daily dose of methadone in 60 patients undergoing methadone maintenance treatment (MMT). Saliva pH was measured immediately after sampling, and concentrations of (RS)-, (R)-, and (S)-methadone in saliva and plasma were assayed by LC/MS. In addition, unbound (R)- and (S)-methadone concentrations were measured in plasma samples by ultrafiltration. Plasma binding and pH differences between plasma and saliva were then used to estimate methadone saliva/plasma ratios and to compare them with observed values. Saliva pH ranged from 5.1 to 7.6 (mean +/- SD, 6.7 +/- 0.5). Plasma and saliva concentrations correlated weakly [(RS)-, r = 0.14, P = 0.007, n = 44; (R)-, r = 0.10, P = 0.04, n = 43; (S)-, r = 0.22, P = 0.002, n = 43], and the mean saliva-to-plasma methadone concentration ratios were 1.1 (+/-1.3 SD), 1.5 (+/-1.5), and 0.8 (+/-0.8), for (RS)-, (R)-, and (S)-methadone, respectively. Corresponding values based on unbound concentrations of methadone in plasma were 21 (+/-20.6, n = 31), 21 (+/-19, n = 34), and 17 (+/-15, n = 36). The salivary concentration-to-dose ratios showed statistically significant but weak inverse correlations with saliva pH [(RS)-, r = 0.27, P < 0.001; (R)-, r = 0.25, P < 0.001; (S)-, r = 0.29, P < 0.001, respectively]. There were significant correlations between predicted and observed saliva/plasma ratios [(RS)-, r = 0.44, P < 0.001, n = 31; (R)-, r = 0.58, P < 0.001, n = 32; (S)-, r = 0.10, P = 0.04, n = 34], but the mean predicted saliva concentrations were about 5 times lower than the mean observed values. The poor correlations between salivary and plasma methadone concentrations observed in this study are partly related to the effect of variable saliva pH. However, saliva pH explained only 10%-36% of the total variation. As a conclusion, monitoring methadone concentrations in saliva may not be a useful alternative to plasma concentration measurements. Correction for saliva pH measured immediately after collection improves the relationship between saliva and plasma methadone concentration, but most of the variation remains unexplained.

journal_name

Ther Drug Monit

journal_title

Therapeutic drug monitoring

authors

Shiran MR,Hassanzadeh-Khayyat M,Iqbal MZ,Lagundoye O,Seivewright N,Lennard MS,Tucker GT,Rostami-Hodjegan A

doi

10.1097/01.ftd.0000164392.01779.db

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

580-6

issue

eissn

0163-4356

issn

1536-3694

pii

00007691-200510000-00008

journal_volume

pub_type

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Can saliva replace plasma for the monitoring of methadone?