Life sciences (1973), 2011-05, Vol.88 (21), p.959-971
2011
Details
- Autor(en) / Beteiligte
- Titel
- Efflux transporters- and cytochrome P-450-mediated interactions between drugs of abuse and antiretrovirals
- Ist Teil von
- Life sciences (1973), 2011-05, Vol.88 (21), p.959-971
- Ort / Verlag
- Netherlands: Elsevier Inc
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Multidrug regimens and corresponding drug interactions cause many adverse reactions and treatment failures. Drug efflux transporters: P-gp, MRP, BCRP in conjunction with metabolizing enzymes (CYPs) are major factors in such interactions. Most effective combination antiretrovirals (ARV) therapy includes a PI or a NNRTI or two NRTI. Coadministration of such ARV may induce efflux transporters and/or CYP3A4 resulting in sub-therapeutic blood levels and therapeutic failure due to reduced absorption and/or increased metabolism. A similar prognosis is true for ARV-compounds and drugs of abuse combinations. Morphine and nicotine enhance CYP3A4 and MDR1 expression in vitro. A 2.5 fold rise of cortisol metabolite was evident in smokers relative to nonsmokers. Altered functions of efflux transporters and CYPs in response to ARV and drugs of abuse may result in altered drug absorption and metabolism. Appropriate in vitro models can be employed to predict such interactions. Influence of genetic polymorphism, SNP and inter-individual variation in drug response has been discussed. Complexity underlying the relationship between efflux transporters and CYP makes it difficult to predict the outcome of HAART as such, particularly when HIV patients taking drugs of abuse do not adhere to HAART regimens. HIV + pregnant women on HAART medications, indulging in drugs of abuse, may develop higher viral load due to such interactions and lead to increase in mother to child transmission of HIV. A multidisciplinary approach with clear understanding of mechanism of interactions may allow proper selection of regimens so that desired therapeutic outcome of HAART can be reached without any side effects.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0024-3205eISSN: 1879-0631DOI: 10.1016/j.lfs.2010.09.012Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3100475
- Format
- –
- Schlagworte
- Analgesics, Opioid - metabolism, Anti-HIV Agents - metabolism, Anti-HIV Agents - therapeutic use, Antiretroviral Therapy, Highly Active, Antiretrovirals agents, ATP Binding Cassette Transporter, Subfamily B, Member 1 - drug effects, ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism, ATP Binding Cassette Transporter, Subfamily G, Member 2, ATP-Binding Cassette Transporters - drug effects, ATP-Binding Cassette Transporters - metabolism, Benzodiazepines - metabolism, Breast cancer resistance protein, Cocaine - metabolism, Cytochrome P-450, Cytochrome P-450 CYP3A - drug effects, Cytochrome P-450 CYP3A - metabolism, Cytochrome P-450 Enzyme System - drug effects, Cytochrome P-450 Enzyme System - metabolism, Drug Interactions, Female, HIV Infections - complications, HIV Infections - drug therapy, Human immunodeficiency virus, Humans, Methamphetamine - metabolism, Multidrug resistance-associated protein, Neoplasm Proteins - drug effects, Neoplasm Proteins - metabolism, P-glycoprotein, Pregnancy, Protease inhibitors and drugs of abuse, Ritonavir - metabolism, Ritonavir - therapeutic use, Substance-Related Disorders - complications