LNSLNS

The considerations of the article on drug interactions apply not only to patients with multimorbidities but also in general.

I agree that the consequences of pharmacokinetic interactions are more pronounced especially among drugs with a narrow therapeutic range. Lithium is a further typical example in this context.

The correspondent’s statement that dexamethasone “seals” the blood-brain barrier and thus inhibits the penetration of the alkylant temozolomide, which is indicated for glioblastoma tumors, lacks evidence. Möhnle et al. discuss non-genomic effects of high-dose dexamethasone on plasma membranes, which would lead to inhibition of the Na+- and K+-fluxes, rather than pharmacokinetic interactions with temozolomide (1). A reduction of the bioavailability of temozolomide in the central nervous system in presence of glucocorticoids has not been described. However, there are in-vitro indications of a pharmacodynamic interaction, albeit one whose effects are negative: it seems that dexamethasone protects human glioblastoma cells from temozolomide induced apoptosis (2, 3).

There are certainly many specific examples that provide an impetus for further discussion; however, our CME article aimed to provide a systematic overview of pharmacokinetic interactions in principle and, in addition, to draw attention to some examples of typical pharmacodynamic interactions that should be considered during therapy.

DOI: 10.3238/arztebl.2013.0133b

Prof. Dr. med. Dr. rer. nat. Ingolf Cascorbi

Institut für Experimentelle u. Klinische Pharmakologie
Universitätsklinikum Schleswig-Holstein, Kiel
cascorbi@pharmakologie.uni-kiel.de

Conflict of interest statement
The authors of all contributions declare that no conflict of interest exists.

1.
Möhnle P, Uhl E, Briegel J: Glukokortikoide in der Neurointensivmedizin – welche Indikationen sind gesichert? J Neurol
Neurochir Psychiatr 2008; 9: 7–12.
2.
Das A, Banik NL, Patel SJ, Ray SK: Dexamethasone
protected human glioblastoma U87MG cells from
temozolomide induced apoptosis by maintaining Bax:
Bcl-2 ratio and preventing proteolytic activities. Mol Cancer 2004; 3: 36 CrossRef MEDLINE PubMed Central
3.
Sur P, Sribnick EA, Patel SJ, Ray SK, Banik NL:
Dexamethasone decreases temozolomide-induced apoptosis
in human gliobastoma T98G cells. Glia 2005; 50: 160–7 CrossRef MEDLINE
4.
Cascorbi I: Drug interactions—principles, examples and
clinical consequences. Dtsch Arztebl Int 2012; 109(33–34): 546–56 VOLLTEXT
1. Möhnle P, Uhl E, Briegel J: Glukokortikoide in der Neurointensivmedizin – welche Indikationen sind gesichert? J Neurol
Neurochir Psychiatr 2008; 9: 7–12.
2. Das A, Banik NL, Patel SJ, Ray SK: Dexamethasone
protected human glioblastoma U87MG cells from
temozolomide induced apoptosis by maintaining Bax:
Bcl-2 ratio and preventing proteolytic activities. Mol Cancer 2004; 3: 36 CrossRef MEDLINE PubMed Central
3. Sur P, Sribnick EA, Patel SJ, Ray SK, Banik NL:
Dexamethasone decreases temozolomide-induced apoptosis
in human gliobastoma T98G cells. Glia 2005; 50: 160–7 CrossRef MEDLINE
4.Cascorbi I: Drug interactions—principles, examples and
clinical consequences. Dtsch Arztebl Int 2012; 109(33–34): 546–56 VOLLTEXT

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