An IVIVC (in vitro-in vivo co-relationship) is a terminology commonly used in the area of drug dissolution testing desiring relationship of in vitro (drug dissolution) results with in vivo characteristics such as drug levels in humans.
As the in vitro results are generally expressed as cumulated percent drug release, thus these profiles (results) are difficult to compare with in vivo results which are reported in concentration units. In addition, in vitro results only reflect release (dissolution) characteristics of a product while in vivo results reflect combined effect of drug dissolution and absorption/elimination characteristics. To achieve appropriate comparison, either the in vitro dissolution results are manipulated (mathematically) using drug absorption/elimination characteristics to predict blood levels and compared with actual/observed drugs levels or by extracting in vivo dissolution results from actual drug levels in humans and to compare with the observed in vitro results. The first approach is known as a convolution technique and the second as de-convolution. One of these techniques of data manipulation would be required to make the results comparable.
Once the desired results are derived i.e. in vivo dissolution from drug levels in blood (de-convolution) or in vivo drug levels from in vitro dissolution tests (convolution), these are compared with corresponding/actual in vitro or in vivo results, respectively. Achieving level A IVIVC means that these comparisons of results be done point by point, i.e., in vitro and in vivo results are compared individually for each sampling time. More accurately plotting in vitro and in vivo results as a line and obtaining a coefficient of relationship (r) value approaching 1. This is where the difficulty is i.e. assumption of exact or matching time course in both in vitro and in vivo drug release. However, this is a well known fact that predictability of accurate time course of drug in humans is very difficult, if not impossible. For example, even when one would like to compare drug levels in humans alone, such as in bioequivalence studies, such point by point comparisons of drug levels are neither used nor required by regulatory agencies. The reason being variability in results (within or between human subjects) is expected to be very high. Therefore, how could it be possible to achieve point by point comparisons of in vitro and in vivo results?
To address this difficulty in comparing the in vivo results for bioequivalence studies, one is required to use derived parameters from the drug levels which are; highest observed drug (concentration) level, and the area under the drug concentration-time profiles. These parameters sort of normalize or reduce the observed variability of drug levels or profiles thus offer a more reasonable approach for the evaluation or comparison of in vivo results.
Thus, in short, one should keep in mind the limitations, in fact impractically, of point by point (Level A) comparison approach for IVIVC purposes. For a more detailed discussion on this aspect, in particular regarding developing IVIVC, one of my publications may be of interest (The Open Drug Delivery Journal, 2010, 4, 38-47, Link).
