The Inhibitory Quotient (IQ)

An alternative approach to interpreting resistance tests is to relate the observed IC50 of an isolate to the achievable trough concentration (Cmin) of drug or to the measured trough concentration of that drug in a particular patient. The relationship between drug exposure and drug susceptibility can be explored through the inhibitory quotient (IQ), which is the Cmin/IC50 ratio. (Many drugs are bound to proteins in the plasma, reducing the effective [free] drug concentration. Therefore, IC50 values used in calculating the IQ are often adjusted for protein binding, but how to make such adjustments is controversial.) A high IQ means that the trough plasma concentration is significantly greater than the amount of drug needed to inhibit the virus in question; a low IQ suggests inadequate drug levels or a highly resistant virus.

One study calculated IQ's for patients receiving ritonavir-boosted indinavir (IDV) therapy for treatment of IDV-resistant virus (25). Phenotypes were predicted from genotypic data using the Virtual Phenotype. Using the Virtual Phenotype and measured trough concentrations of IDV to calculate a "virtual" IQ, the investigators found that response rates were significantly higher among patients with an IQ>2 as compared to those with an IQ<2 (P<0.003).

These results suggest that combining phenotypic data with drug levels might be particularly useful in predicting treatment response. However, adjusting drug doses on the basis of the IQ in an attempt to overcome drug resistance may not be advisable, since the safety of very high drug levels that might be required in certain cases has not been evaluated.

4/15/01

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