Dinalbuphine sebacate

Dinalbuphine sebacate

Clinical data
Other names	DNS; Nalbuphine sebacate; Sebacoyldinalbuphine; SDN; Sebacoyl dinalbuphine ester; SDE; LT-1001
Routes of administration	Intramuscular injection
Drug class	Opioid analgesic
Pharmacokinetic data
Bioavailability	• IM: 85.4% (relative to nalbuphine)
Metabolism	Hydrolysis
Metabolites	Nalbuphine
Elimination half-life	• DNS: 83.2 hours (mean absorption time: 145.2 hours) • Nalbuphine: 4.0 hours
Identifiers
IUPAC name Bis[(4R,4aS,7S,7aR,12bS)-3-(cyclobutylmethyl)-4a,7-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-9-yl] decanedioate
CAS Number	311768-81-7
PubChem CID	9962795
ChemSpider	8138394
UNII	464OXX39Y6
ChEMBL	ChEMBL1823241
Chemical and physical data
Formula	C52H68N2O10
Molar mass	881.120 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1CC(C1)CN2CC[C@]34[C@@H]5[C@H](CC[C@]3([C@H]2CC6=C4C(=C(C=C6)OC(=O)CCCCCCCCC(=O)OC7=C8C9=C(C[C@@H]1[C@]2([C@]9(CCN1CC1CCC1)[C@@H](O8)[C@H](CC2)O)O)C=C7)O5)O)O
InChI InChI=1S/C52H68N2O10/c55-35-19-21-51(59)39-27-33-15-17-37(45-43(33)49(51,47(35)63-45)23-25-53(39)29-31-9-7-10-31)61-41(57)13-5-3-1-2-4-6-14-42(58)62-38-18-16-34-28-40-52(60)22-20-36(56)48-50(52,44(34)46(38)64-48)24-26-54(40)30-32-11-8-12-32/h15-18,31-32,35-36,39-40,47-48,55-56,59-60H,1-14,19-30H2/t35-,36-,39+,40+,47-,48-,49-,50-,51+,52+/m0/s1 Key:ALOIOAGKUOQNID-ITCIXCFHSA-N

Dinalbuphine sebacate (DNS), also known as nalbuphine sebacate or as sebacoyl dinalbuphine ester (SDE) and sold under the brand name Naldebain, is a non-controlled opioid analgesic which is used as a 7-day long-acting injection in the treatment of moderate to severe postoperative pain.

The compound is a diester of nalbuphine (Nubain) joined via a sebacic acid linker, and acts as a long-lasting prodrug of nalbuphine via slow hydrolysis. It was developed to extend the duration of action of nalbuphine, which has a short duration and requires frequent injections. Whereas nalbuphine must be injected every 4 to 6 hours, a single injection of DNS lasts for up to 7 to 10 days.

It was invented by professor Oliver Yoa-Pu Hu (National Defense Medical Center) and codeveloped with Lumosa Therapeutics. Naldebain received market approvals from Taiwan FDA in March 2017, Health Sciences Authority of Singapore in December 2020, the Ministry of Public Health of Thailand in December 2021, and the Drug Control Authority of Malaysia in 2022. Development is ongoing in the United States, China, Korea, Ukraine, the Philippines, and Brunei.

Medical uses

Naldebain is indicated for the relief of moderate to severe acute postsurgical pain, administered intramuscularly. The product is available in single-use vials; 2 mL single use vial (75 mg/mL) for IM injection is packaged in a carton.

Pack shot of Naldebain

Pharmacology

Pharmacodynamics

Nalbuphine, and hence DNS, acts as a mixed agonist/antagonist opioid modulator, or more specifically as a moderate-efficacy partial agonist or antagonist of the μ-opioid receptor and as a high-efficacy partial agonist of the κ-opioid receptor.

Pharmacokinetics

The release mechanism of dinalbuphine sebacate (DNS) upon IM injection is as follows:

1. The injected Naldebain is first forming an oil depot in the muscle
2. The oil depot gradually dispersed to small droplets in the surrounding tissues
3. The prodrug DNS diffused out from the surface of oil droplets, and once released, a small portion of the prodrug get hydrolyzed by esterases to release the active ingredient, nalbuphine, in the surrounding tissue cells, while the majority of the prodrug would enter the blood stream through local tissue drainage (e.g., lymph flow) and get hydrolyzed to nalbuphine in the blood.

External links

• Dinalbuphine sebacate - AdisInsight
• Naldebain information - Lumosa Therapeutics website