Human accumulation potential of xenobiotics: potential of catamphiphilic drugs to promote their accumulation via inducing lipidosis or mucopolysaccharidosis
| Autor: | Klaus Mohr, L Hein, Renate Lüllmann-Rauch |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Drug
medicine.medical_specialty Health Toxicology and Mutagenesis media_common.quotation_subject Mucopolysaccharidosis Phospholipid Biology Lipidoses Toxicology Biochemistry Inclusion bodies Xenobiotics Glycosaminoglycan chemistry.chemical_compound Pharmacokinetics Internal medicine medicine Humans Tissue Distribution Receptor Glycosaminoglycans media_common Pharmacology Lipid metabolism General Medicine Mucopolysaccharidoses Lipid Metabolism medicine.disease Endocrinology chemistry Lysosomes |
| Zdroj: | Xenobiotica. 20:1259-1267 |
| ISSN: | 1366-5928 0049-8254 |
| Popis: | 1. Drug accumulation without a concomitant elevation of blood level may occur if the capacity of the tissue to bind drug increases during chronic treatment. 2. This special type of accumulation is found with cationic-amphiphilic drugs, which induce the formation of lysosomal inclusion bodies containing undergraded lipids or mucopolysaccharides (drug-induced lipidosis or mucopolysaccharidosis, respectively); the stored material provides the additional binding sites for the drug. 3. Factors determining the potential for inducing lipidosis or mucopolysaccharidosis are: (a) affinity of the drugs to phospholipid layers (governed by hydrophobicity) or mucopolysaccharides (drug-induced lipidosis or mucopolysaccharidosis, respectively); the free intra-lysosomal concentration, which is elevated compared with the blood level due to lysosomal trapping (especially with dicationic drugs); (c) the therapeutically required drug concentration in the blood: the therapeutic concentrations are high with drugs that do not act via binding to specific high-affinity receptors. |
| Databáze: | OpenAIRE |
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