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Ullrich Kleeberg

Publications and source records attributed to Ullrich Kleeberg.

2 recordsLinked to original sources

Pharmacogenetics-based new therapeutic concepts.

Pharmacogenetics, one of the fields of clinical pharmacology, studies how genetic factors influence drug response. If hereditary traits are taken into account appropriately before starting drug treatment, the type of drug and its dosage can be tailored to the individual patient's needs. Pharmacogenetics adds a considerable amount of stringency to the doctor's therapeutic approach. Today, it is the relationship between dosage requirements and genetic variations in drug metabolizing enzymes like cytochrome P450 (CYP) 2D6 and CYP2C19, or in drug transporters like p-glycoprotein, that is substantiated best. A standard dose will bring about more adverse effects than usual if enzymatic activity is lacking or feeble. Sometimes, however, therapeutic response might be better due to higher concentrations: proton pump inhibitors for eradication of Helicobacter pylori are more efficacious in carriers of a deficient CYP2C19 variant. The drug's interaction with its target (e.g. receptor) also depends on genetic factors. In some cases genetic tests can help distinguish between responders and non-responders of a specific drug treatment. The first pharmacogenetic tests are already on the market.

Animals↗

Differential drug-induced mRNA expression of human CYP3A4 compared to CYP3A5, CYP3A7 and CYP3A43.

Drug-mediated regulation of mRNA expression of all members of the cytochrome P450 3A (CYP3A) subfamily has been measured by reverse transcription-polymerase chain reaction (RT-PCR) in the human hepatocellular carcinoma cell line, HepG2. Transcriptional regulation was proved by inhibition of induction with actinomycin D. Besides the positive control dexamethasone, the H(+)/K(+)-ATPase inhibitors omeprazole, lansoprazole, pantoprazole, and rabeprazole, and the herbal antidepressant St. John's wort (Hypericum extract) were studied. All CYP3A mRNAs were induced by dexamethasone. CYP3A4 was the only CYP3A isoform that was induced by all of the four benzimidazole derivatives, while CYP3A5, CYP3A7, and CYP3A43 were unaffected or even slightly downregulated by these drugs. St. John's wort also increased CYP3A4 mRNA exclusively, leaving CYP3A5 and CYP3A43 unaffected, whereas CYP3A7 was decreased. Depending on the inducer, expression of CYP3A4 is differently regulated from CYP3A5, CYP3A7, and CYP3A43.

2-Pyridinylmethylsulfinylbenzimidazoles↗