PharmPK Discussion - Doxorubicin

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On 4 Mar 2001 at 21:21:29, "Unn-Merete Fagerli" (unnmf.-a-.online.no) sent the message


Hi,

I am an oncologist interested in pharmacology, and especially in TDM
(therapeutic drug monitoring) of doxorubicin. Does anyone know a
method and/or has practical experience in this issue? I would be
pleased to hear about it.

Unn-Merete Fagerli

Dept.Oncology

Trondheim University Hospital, Norway

unnmf.-at-.online.no

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On 9 Mar 2001 at 10:53:24, Georg Hempel (hempege.-at-.uni-muenster.de) sent the message


Hello,

in our lab, we quantify doxorubicin in plasma samples from children.
We use capillary electrophoresis with laser-induced fluorescence
detection. ( Hempel G, Schulze Westhoff P, Flege S, Laubrock N, Boos J.
Therapeutic drug monitoring of doxorubicin in paediatric oncology using
capillary electrophoresis. Electrophoresis 19: 2939-2943, 1998 )
The method is very useful when only small sample volumes are available.

Otherwise, HPLC with fluorescence detection can be used, see for
example:
Jacquet, J.M., Galtier, M., Bressolle, F., Jourdan, J., J. Pharm.
Biomed. Anal. 1992, 10, 343-348.
Camaggi, C.M., Comparsi, R., Strocchi, E., Testoni, F., Pannuti, F.,
Cancer Chemother. Pharmacol. 1988, 21, 216-220.
Beijnen, J.H., Meenhorst, P.L., Van Gijn, R., Fromme, M., Rosing, H.,
Underberg, W.J.M., J. Pharm. Biomed. Anal. 1991, 9, 995-1002

However, our initial results indicate that dose individualisation based
on plasma concentration measurements does not make sense due the high
intra-individual variability, which often (in many patients) exceeds the
inter-individual variability.

As far as I know, TDM with dose individualisation for anthracyclines has
often been suggested  but never been done sucessfully.
It has been questioned if the PLASMA concentrations of anthracyclines
are a useful parameter for the drug effect at all or if whole blood
levels are a better parameter because of  the high intracellular
concentrations of the drugs.
Also, a lot of work has been done with the intracellular concentrations
of anthracyclines in patients with leukaemia. However, there is no
evidence that dose adaption based on the intracellular concentrations
can improve the response and safety of anthracycline therapy.

I hope that this helps,

Georg Hempel

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