Disease relevance of Drug Interactions

• The cytotoxicity of vincristine (VCR), beta-cytosine arabinoside (Ara-C), or adriamycin (ADRIA) in combination with 5-azacytidine (Aza-CR) to L1210 leukemia in vivo was measured to determine if schedule-dependent synergistic or antagonistic drug interaction occurred [1].
• Although the use of twice weekly oral methotrexate may have been a causative factor, a previously unsuspected drug interaction with etoposide may be the etiologic factor resulting in this unusually high incidence of pulmonary toxicity [2].
• Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New Approaches to Brain Tumor Therapy Central Nervous System Consortium [3].
• Because of drug interactions, pravastatin may represent the preferred choice in those taking HIV protease inhibitors [4].
• Cimetidine causes a small number of adverse effects, including neuropsychiatric disorders, gynecomastia, impotence, loss of libido, elevation of serum creatinine and serum transaminases concentrations, and drug interactions [5].

Psychiatry related information on Drug Interactions

• Indinavir is being studied as a twice daily and once daily regimen with a low dosage of ritonavir as a way to alleviate tolerability, drug interaction and patient compliance/adherence issues [6].
• CONCLUSION: We suggest that, in patients with mental retardation and epilepsy, involuntary movements may either occur as reversible side effects of gabapentin therapy or result from a previously undescribed adverse drug interaction with other antiepileptic agents [7].
• In contrast, concomitant medication with various drugs with rivastigmine does not seem to cause any drug interactions in patients with Alzheimer's disease [8].
• Furthermore, moclobemide lacks significant effects on psychomotor performance and cognitive function, has few clinically important drug interactions and is safe on overdose [9].
• OBJECTIVE: The purpose of this review was to summarize the background on dementia of the Alzheimer type and the pharmacokinetic properties, efficacy and tolerability profiles, clinical applications, adverse effects (AEs), drug interactions, and pharmacoeconomics of rivastigmine [10].

High impact information on Drug Interactions

• Drug interaction between thyroxine and lovastatin [11].
• Possible drug interaction during therapy with azidothymidine and acyclovir for AIDS [12].
• A digoxin-antibiotic drug interaction [13].
• Adenine arabinoside and allopurinol--possible adverse drug interaction [14].
• Saralasin, an angiotensin antagonist, was used to study the role of renin-angiotensin in the vasodilator-beta-blocker drug interaction in hypertensive subjects [15].

Chemical compound and disease context of Drug Interactions

• Although we have failed to explain the underlying mechanism of this drug interaction, our data suggest that allopurinol may increase the antitumor activity of cyclophosphamide without increasing its bone marrow toxicity [16].
• Apparent quinidine-induced digoxin toxicity after withdrawal of pentobarbital: a case of sequential drug interactions [17].
• Digoxin toxicity and ritonavir: a drug interaction mediated through p-glycoprotein [18]?
• Four case reports have been published that document a clinically significant drug interaction between nifedipine and quinidine in patients with left ventricular dysfunction [19].
• Given the limited bioavailability of saquinavir given in the hard gelatin capsule formulation, this drug interaction is expected to have implications in the use of protease inhibitors in the management of human immunodeficiency virus infection [20].

Biological context of Drug Interactions

• The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions [21].
• This observation was interpreted as a drug interaction: valproic acid competed with phenytoin for access to plasma protein binding sites [22].
• Evaluation of drug interactions with isobolograms showed that at near-serum levels, carboplatin or cisplatin interacted synergistically with 1,25(OH)2D3 to inhibit MCF-7 cell growth [23].
• Pharmacokinetics of gyrase inhibitors, Part 2: Renal and hepatic elimination pathways and drug interactions [24].
• Database searches combined the keyword warfarin with drug interactions, herbal medicines, Chinese herbal drugs, and food-drug interactions [25].

Anatomical context of Drug Interactions

• In conclusion, the bioartificial liver composed of human functional HCC cell line was useful in studying drug interactions during induction of human CYP3A4 [26].
• A group by drug interaction was observed in the anterior cingulate gyrus, where nicotine decreased activity in control subjects and increased activity in schizophrenic subjects [27].
• This study examined LAAM and nor-LAAM metabolism using human liver microsomes, cDNA-expressed CYP, CYP isoform-selective chemical inhibitors, and monoclonal antibody to determine kinetic parameters for predicting in vivo drug interactions, involvement of constitutive CYP isoforms, and mechanistic aspects of sequential N-demethylation [28].
• Intestinal drug metabolism and countertransport into the gut lumen, drug interactions with CYP3A substrates and inhibitors in the small intestine and an 8-fold interindividual variability of the intestinal metabolite formation rate significantly contribute to the low and highly variable bioavailability of sirolimus [29].
• Reversal of acquired resistance to adriamycin in CHO cells by tamoxifen and 4-hydroxy tamoxifen: role of drug interaction with alpha 1 acid glycoprotein [30].

Associations of Drug Interactions with chemical compounds

• We investigated the possibility of a drug interaction between the antilipemic agent halofenate and sulfonylureas [31].
• Membrane surface potential changes may alter drug interactions: an example, acetylcholine and curare [32].
• Drug interactions at the GABA receptor-ionophore complex [33].
• We conclude that the combination of erythromycin and carbamazepine represents a clinically significant drug interaction and should be avoided where possible [34].
• Dosage restriction and awareness of the clinical conditions and drug interactions capable of inhibiting the metabolism of terfenadine are essential for prevention of this serious reaction [35].

Gene context of Drug Interactions

• Although expression of the CYP3A4 gene is known to be induced in response to a variety of compounds, the mechanism underlying this induction, which represents a basis for drug interactions in patients, has remained unclear [21].
• The development and use of P-gp inhibitors with minimal or absent CYP3A inhibitory effects should decrease the impact of drug interactions on the therapeutic use of such compounds [36].
• In this manner, induction of CYP3A5 may contribute to the overall importance of this P450 in drug metabolism and drug interactions [37].
• Interindividual variability and drug interactions affecting intestinal transporter and hepatic CYP3A and CYP2B6 activity may alter methadone disposition [38].
• In conclusion, activation of PXR and CAR and especially the resulting induction of CYP3A4 and MDR1 demonstrate that artemisinin has a higher risk of potential drug interactions than anticipated previously [39].

Analytical, diagnostic and therapeutic context of Drug Interactions

• An oral heparin formulation would avoid the inconvenience of subcutaneous injection and the unfavorable drug interactions and adverse events associated with warfarin [40].
• An understanding of the nature of the individual cytochrome P450 enzymes and their regulation should be useful in determining the most suitable animal models, ascertaining risk from chemicals, and in avoiding undesirable drug interactions [41].
• The current investigation evaluated a potential drug interaction between the angiogenesis inhibitor O-(N-chloroacetyl-carbamoyl)-fumagillol (TNP-470) and the alkylating agent temozolomide (TMZ), in xenograft models that differentially expressed vascular endothelial growth factor (VEGF), a driving force for angiogenesis [42].
• Absence of drug interaction between heparin and nitroglycerin. Randomized placebo-controlled crossover study [43].
• Clinical trials combining tamoxifen with letrozole or anastrazole have shown minor pharmacokinetic drug interactions [44].

References