Anesthetic/sedative of the future
Similar to its analgesic sibling remifentanil, Byfavo represents another member of the soft drug class, featuring favorable pharmacokinetic profile.
It provides a softer, faster & cleaner general anesthetic/sedative for anesthesiologists & patients undergoing general anesthesia, procedural sedation, and ICU sedation beyond 24 hours.
I. Soft Byfavo
Soft drug design represents a new approach aimed to design safer drugs with an increased therapeutic index by integrating metabolism considerations into the drug design process.
They are therapeutic agents that undergo predictable metabolism to convert into inactive metabolites after exerting their therapeutic effect.
They are designed by building into the molecule, in addition to the activity, the most desired way in which the molecule is to be deactivated and detoxified.1]
Byfavo was developed with this soft drug design in mind, modifying a known drug to create an analogue with improved pharmacokinetic properties
The development process of Byfavo Inj. included adding a metabolically labile ester moiety to a structure derived from the benzodiazepine class. This modification allowed Byfavo to be Inj.highly susceptible to hydrolysis by tissue esterases.7]
The methyl ester undergoes dose-independent ester hydrolysis and converts Byfavo into its inactive metabolite, CNS 7054. 2]
II. Fast Byfavo
Aspects of soft drugs designs that are particularly interesting to anesthesiologists include rapid onset of effect and quick recovery. 3]
Byfavo is an ultra-short acting anesthetic agent/sedative that is rapidly metabolized to an inactive metabolite by CES1, one of the predominant drug metabolizing enzymes of liver and other organs, e.g. kidney, brain, lung. 7,8]
Its clever design results in fast onset, a short-predictable duration of sedative action, and a more rapid recovery profile than older sedatives of the benzodiazepine class currently available on the market. 4]
The plasma clearance of Byfavo is approximately three times faster than the clearance of midazolam. 2]
Byfavo has a rapid CSHT (Context-Sensitive Half-Time) of 7 min, for a continuous IV infusion of up to 4 hours. 10]
The CSHT profile for Byfavo is similar to remifentanil even for infusions up to 8 hours.
III. Clean Byfavo
Byfavo shows high extrahepatic clearance, and since its metabolism does not rely on cytochrome enzymes, metabolic interactions with other drugs in the liver is limited. 7]
A Phase I trial confirmed its safety even in Japanese patients with mild to moderate hepatic disorders. 11]
Also in general anesthesia, no dose adjustment was necessary even in patients with end-stage renal disease. 11]
Availability of a specific antagonist (flumazenil, Lumasate Inj, Hana Pharm) further verifies Byfavos’ cleanness and safety, in case of overdose.
It offers a broad therapeutic window for induction and maintenance of general anesthesia, with no residual effects observed after awakening.
Its neutralization by an enzyme present in extrahepatic tissues decreases the likelihood of drug accumulation, and thus decrease occurrence of syndromes like "propofol infusion syndrome". 2,9]
Unparalleled Novelty of Byfavo "Independency"
1. Organ-independent elimination: Byfavo can be administered safely in patients with hepatic or renal impairment. 2,11]
2. Dose-independent ester hydrolysis: Byfavo is converted into its inactive metabolite, CNS7054, rapidly. 2]
3. Body-weight-independent systemic clearance (model-independent clearance). 5]
4. 4. Infusion duration (up to 4 hours) independent rapid CSHT (7 minutes). 3]6]10]
5. Metabolic inactivation mediated by carboxylesterase 1 and independent of liver cytochrome system. 7]