PubMed · 5763111
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J A Owen. 1969. Drug interactions.. https://pubmed.ncbi.nlm.nih.gov/5763111/
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The joint action of soil-applied herbicide mixtures with similar or different modes of action has been assessed by using the additive dose model (ADM). The herbicides chlorsulfuron, metsulfuron-methyl, pendimethalin and pretilachlor, applied either singly or in binary mixtures, were used on rice (Oryza sativa L.). The growth (shoot) response curves were described by a logistic dose-response model. The ED50 values and their corresponding standard errors obtained from the response curves were used to test statistically if the shape of the isoboles differed from the reference model (ADM). Results showed that mixtures of herbicides with similar molecular targets, i.e. chlorsulfuron and metsulfuron (acetolactate synthase (ALS) inhibitors), and with different molecular targets, i.e. pendimethalin (microtubule assembly inhibitor) and pretilachlor (very long chain fatty acids (VLCFAs) inhibitor), followed the ADM. Mixing herbicides with different molecular targets gave different results depending on whether pretilachlor or pendimethalin was involved. In general, mixtures of pretilachlor and sulfonylureas showed synergistic interactions, whereas mixtures of pendimethalin and sulfonylureas exhibited either antagonistic or additive activities. Hence, there is a large potential for both increasing the specificity of herbicides by using mixtures and lowering the total dose for weed control, while at the same time delaying the development of herbicide resistance by using mixtures with different molecular targets.
Despite the fact that the combination of vancomycin and a beta-lactam antibiotic are known to act synergistically on vancomycin-susceptible Staphylococcus aureus (VSSA), some MRSA have emerged showing antagonism to the combination of vancomycin and a beta-lactam antibiotic. These MRSA are called beta-lactam antibiotic-induced vancomycin resistant MRSA (BIVR). A method based on this antagonistic phenomenon has been devised to detect BIVR strains. The method inhibits the VSSA strain but allows the BIVR strain to grow. Forty-six commercially available beta-lactam antibiotics induced the vancomycin-resistance. Using this detection method, 717 MRSA clinical isolates obtained from eight institutes throughout Japan were thus screened and 6.3% of these were detected as BIVR when judged at 48 h.
1: The inhibition kinetics of eplerenone (EP) 6beta-hydroxylation by 10 drugs were determined in vitro using human liver microsomes. Inhibition factors were calculated from in vitro inhibition constant (Ki) and three different inhibitor Cmax values (liver Cmax of total and unbound inhibitor, and maximum influx concentration of inhibitor into the liver). Subsequently, the inhibition factors were compared with available pharmacokinetic data derived from clinical interaction trials conducted by Pfizer involving EP and these drugs. EP was also evaluated for its effect on the metabolism of 10 drugs in vitro, and again the in vitro data were compared with results from the clinical trials. 2: The Ki values for the inhibition of EP 6beta-hydroxylation by cisapride, cyclosporine, digoxin, erythromycin, fluconazole, ketoconazole, midazolam, saquinavir, simvastatin and verapamil were 2.90, 1.24,>75.0, 9.50, 59.0, 0.160, 8.10, 0.546, 6.23 and 13.3 microM, respectively. Among the three methods, inhibition factors (Rb) calculated using the Ki and estimated liver Cmax values of the unbound drug were best correlated with the in vivo area under the curve-fold increases of EP in humans. The Rb values for the drugs listed above were 1.04, 1.69, 1.00, 2.17, 2.24, 4.90, 1.00, 1.82, 1.01 and 1.04, respectively, and the in vivo area under the curve-fold increases of EP by these drugs were 1.04, 1.16, 0.930, 2.87, 2.24, 5.39, 1.00, 2.07, 1.03 and 1.98, respectively. 3: EP did not have any significant effects on the drugs tested in vitro or in the clinic. 4: Using in vitro metabolic interaction data, human in vivo pharmacokinetic interactions involving EP could be predicted nearly quantitatively. The lack of effects of EP on the pharmacokinetics of other drugs in man was also suggested in the in vitro data.