Dorio Mechanism of Action

Pharmacology: Pharmacodynamics: Doripenem belongs to the carbapenem class of antimicrobials with in vitro antibacterial activity against aerobic and anaerobic, gram-positive and gram-negative bacteria. Doripenem exerts its bactericidal activity by inhibiting bacterial cell wall biosynthesis. Doripenem inactivated multiple essential penicillin-binding proteins (PBPs), resulting in inhibition of cell wall synthesis with subsequent cell death. In Escherichia coli and Pseudomonas aeruginosa, doripenem binds to penicillin-binding protein 2, which is involved in the maintenance of cell shape, as well as to penicillin-binding protein 3 and 4.
Pharmacokinetics: Absorption: The pharmacokinetics of doripenem (maximal drug concentration (C_max) and area under the concentration-time curve (AUC)) are linear over a dose range of 500 mg to 1 g when IV infused over 1 hour. There is no accumulation of doripenem following multiple IV infusions of 500 mg or 1 g administered every 8 hours for 7 to 10 days in subjects with normal renal function.
Distribution: The average binding of doripenem to plasma protein is approximately 8.1% and is independent of plasma drug concentrations. The median volume of distribution at steady state in healthy adults is 16.8 L, similar to extracellular fluid volume (18.2 L).
Metabolism: Doripenem is partially metabolized to a microbiologically inactive ring-opened metabolite (doripenem-M1) primarily via dehydropeptidase-1. The mean plasma doripenem-M1 to doripenem AUC ratio following single 500 mg and 1 g doses in healthy subjects is 18%.
Excretion: Doripenem is primarily eliminated unchanged by the kidneys and undergoes both glomerular filtration and active tubular secretion. The mean plasma terminal elimination half-life of doripenem in healthy nonelderly adults is approximately 1 hour and mean plasma clearance is 15.9 L/h. Mean renal clearance is 10.8 L/h.