Let's consider two drugs, 'A' and 'B'. 'A' has a dose X and 'B' has a dose Y which give individual therapeutic activity. They are combined to produce Synergism to treat a particular disease. My question is, during the formulation of a combinational drug (A & B) should I have to reduce the dose of each drug(s) to attain synergism or formulate a combination with same X and Y (concentration) without any dose reduction? Kindly clarify.
As synergism potentiates the actions of other drugs, hence dosage should be carefully administered considering all type of drug interactions.
So there will be chances of changing(altering) the dose of the drugs, Am I right? Mr. @Atreyee Sarkar
The synergistic effects of drugs usually depends on the pharmacodynamics of the drugs. So their compounded effects are dependent in having adequate quantities of the drugs are the receptor sites. So the drug dosages may actually remain the same as when used individually. For example penicillins with gentamicin work synergistically but at the usual doses. Although they are not a combined formulation. However, dose modification may be required if the drugs have pharmacokinetic interactions. For example if the drugs cause induction of metabolism, excretion or reduction in absorption in the gut, both drugs A and B may have to be increased to reach optimal drug concentrations at the receptors.
The opposite will be true if the drugs cause inhibition of their metabolism. In which case the drugs A and B would both be reduced by the expected level of drug inhibitions. In other cases only one drug may be affected and adjusted , while the other drug remains the same. The way ritonivir is used to reduce metabolism of some other Protease inhibitors; reducing the dose requirements of the PI. However, most newer drugs try to avoid drug interactions because of the wide variability in the response among patients. Which poses a problem in a fixed drug combination if the drug concentration at the receptor sites is less or more than expected. Especially for drugs that may cause induction of some cytochrome enzymes, but inhibition of others.
So each situation is unique and dependent on the pharmacodymics and pharmacokinetics of each individual drugs. As well as the therapeutic index, which affects the safety and patients' abilities to tolerate alterations of drug concentrations at the receptor sites. Drugs with a wide therapeutic window may be left unaltered despite having potention drug-drug interactions.
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