-
1971
As part of the ongoing program at MRL, soil samples from around the world were sent to the company's research laboratory in Madrid, Spain to be tested for the detection of new antibiotics. A technician found a microorganism that responded positively to a screen in a soil sample from New Jersey. The microorganism (named MA4297) was sent to MRL in Rahway, where it was re-grown in fermentation broths and tested, using primary and secondary screens. -
1972
Preliminary tests and screens show a compound produced by MA4297is a beta-lactam antibiotic with broad spectrum of activity against both gram-positive and gram-negative bacteria. It is also showed activity against beta lactamse, an enzyme that inactivates many beta-lactam antibiotics causing antibiotic resistance. Isolation procedures begin. -
1973
Researchers isolate the compound, although still impure, which yields outstanding antibiotic activity. In vivo testing reveals that the compound is nontoxic in animalsindicating it may be appropriate for use in humans. -
1974
The antibiotic is finally isolated, in its purest form, after a special purification technique is used. The chemical structure of the pure compound is determined and called thienamycin. Thienamycin is found to be chemically unstable. -
1975
Merck assigns a team of chemists to make synthetic derivatives of thienamycin that are more stable. Of a series of stabilized semi-synthetic derivatives, the N-formimidoyl derivative called imipenem is selected for further development. Imipenem retains the antibacterial activity of its parent thieanamycin, but is stable enough in solution for clinical applications. Imipenem, however, proves susceptible to degradation by dehydropeptidase enzyme, an enzyme found in the kidneys. Merck discove -
Period: to
Human testing
Human testing begins -
1984
An NDA is submitted to the FDA. Merck begins to market PRIMAXIN/TIENAM in Germany, Austria and Switzerland -
1985
PRIMAXIN I.V. is approved by the FDA.