Steady state concentrations of the enantiomers of mianserin and desmethylmianserin in poor and in homozygous and heterozygous extensive metabolizers of debrisoquine
Articolo
Data di Pubblicazione:
1998
Citazione:
Steady state concentrations of the enantiomers of mianserin and
desmethylmianserin in poor and in homozygous and heterozygous extensive
metabolizers of debrisoquine / C. Eap, C. Lima, F. Macciardi, B. Woggon, K. Powell, P. Baumann. - In: THERAPEUTIC DRUG MONITORING. - ISSN 0163-4356. - 20:1(1998), pp. 7-13.
Abstract:
Steady state concentrations of (S)- and (R)-mianserin and
desmethylmianserin were measured in 21 homozygous extensive metabolizers
(as determined by genotyping for mutations 3 {[or A] and 4 [or B]),
in seven heterozygous extensive metabolizers and in one poor metabolizer
of debrisoquine, as well as in one patient receiving very high doses of
mianserin (360 mg/day) and fluoxetine (160 mg/day), a strong cytochrome
P450IID6 inhibitor. The mean dose of mianserin was (mean +/- SD, range:
67 +/- 63, 10 to 360 mg/day). High dispersions of the (S)/(R)-mianserin
and desmethylmianserin ratios were observed (mean +/- SD, range: 2.10
+/- 1.01, 0.64 to 4.76, and 0.29 +/- 0.14, 0.08 to 0.57, respectively).
The highest (S)/(R)-mianserin ratio was calculated for the poor
metabolizer (4.76) agreeing with those results of a single-dose study
with poor and extensive metabolizers of debrisoquine, in that the
cytochrome P450IID6 is probably involved in the metabolism of mianserin
with an enantioselectivity for the (S)-enantiomer. Nevertheless, the
mean concentration-to-dose ratios for (S)- or (R)-mianserin or
desmethylmianserin were not significantly different between homozygous
and heterozygous extensive metabolizers, and no particular values were
measured in the poor metabolizer nor in the patient receiving
fluoxetine. Furthermore, the (S)/(R)-mianserin ratio measured in the PM
was only slightly higher than the second highest ratio (3.85) of an
homozygous extensive metabolizer, whereas no particular value (2.92) was
calculated for the patient taking fluoxetine. Finally, no significant
differences in (S)/(R)-mianserin or (S)/(R)-desmethylmianserin were
calculated between homozygous and heterozygous extensive metabolizers.
Although the number of patients included in this study is too low to
allow definite conclusions, the results suggest that the debrisoquine
genotype has only a moderate influence on the steady state
concentrations of the enantiomers of mianserin and desmethylmianserin.}
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
CYP2D6; Enantiomer; Mianserin; Steady state concentrations
Elenco autori:
C. Eap, C. Lima, F. Macciardi, B. Woggon, K. Powell, P. Baumann
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