The value of comparative bioavailability studies of marketed drugs in drug control. An example with erythromycin stearate.

As a part of the quality control of drugs The National Medicine Control Laboratory in Finland has started comparative bioavailability studies of synonym preparations in human volunteers by taking all the products containing the same active ingredients for absorption studies at the same time. The first study, which is presented as an example of the importance of these studies, covered three erythromycin stearate preparations containing 250 mg of erythromycin. 12 volunteers took 2 tablets of every product at one week intervals in a cross-over fashion, and the serum erythromycin levels were measured microbiologically for 12 hr. Disintegration and dissolution tests were also performed. One of the products was coated with an acid-resistant film and was not dissolved in pH 1.2, whereas the conventional tablets lost all antimicrobial activity after 15 min in pH 1.2. In phosphate buffer, pH 6.6, all the tablets dissolved rapidly and retained antimicrobial activity. One of the conventional tablets showed only a 50% bioavailability as compared to the two others and was subsequently withdrawn from the market. Thus, it is important to conduct comparative post-marketing bioavailability studies with drugs which earlier have shown good bioavailability.