Consequently, dextroamphetamine produces roughly three to four times more central nervous system (CNS) stimulation than levoamphetamine; however, levoamphetamine has slightly greater cardiovascular and peripheral effects. Related endogenous compounds
Amphetamine has a very similar structure and function to the endogenous trace amines, which are naturally occurring neuromodulator molecules produced in the human body and brain. Among this group, the most closely related compounds are phenethylamine, the parent compound of amphetamine, and N-methylphenethylamine, an isomer of amphetamine (i.e., it has an identical molecular formula). In humans, phenethylamine is produced directly from L-phenylalanine by the aromatic amino acid decarboxylase (AADC) enzyme, which converts L-DOPA into dopamine as well. In turn, N-methylphenethylamine is metabolized from phenethylamine by phenylethanolamine N-methyltransferase, the same enzyme that metabolizes norepinephrine into epinephrine. Like amphetamine, both phenethylamine and N-methylphenethylamine regulate monoamine neurotransmission via TAAR1; unlike amphetamine, both of these substances are broken down by monoamine oxidase B, and therefore have a shorter half-life than amphetamine. Pharmacokinetics
The oral bioavailability of amphetamine varies with gastrointestinal pH; it is well absorbed from the gut, and bioavailability is typically over 75% for dextroamphetamine. Amphetamine is a weak base with a pKa of 9.9; consequently, when the pH is basic, more of the drug is in its lipid soluble free base form, and more is absorbed through the lipid-rich cell membranes of the gut epithelium. Conversely, an acidic pH means the drug is predominantly in a water-soluble cationic (salt) form, and less is absorbed. Approximately 20% of amphetamine circulating in the bloodstream is bound to plasma proteins.
Phase II and III
Treatment-related adverse effects in AOE studies were determined in phase II and III trials. This includes ear pruritus, ear debris, superimposed ear infection, ear congestion, ear pain, and erythema. Similar effects were demonstrated in AOMT studies. Overall, Ciprodex was determined as a safe and well-tolerated drug for the treatment of AOE and AOMT. The proposed dosage for all patients was also effective and safe. Cure rates for pediatrics were slightly higher than adults in AOE studies. Drug interactions
Drug interactions have not been studied with Ciprodex. Commercialization
Ciprodex, owned by Alcon Laboratories, Inc., is protected by multiple patents and will be restricted from generic manufacturing until 2025. Ciprodex is the number 1 topical antibiotic ear drop prescribed since 2007 by ENTs and pediatricians. There have been 18 million prescriptions filled for Ciprodex since 2003, making it the world leading marketed ear drops for AOE.In October 2015, Alcon sued Dr. Reddys Laboratories (DLR) for allegedly infringing on Ciprodex patents. A judge in the UK upheld the Alcon patent. References
External links
"Ciprofloxacin mixture with dexamethasone". Drug Information Portal. U.S. National Library of Medicine.