Details of the Drug

General Information of Drug (ID: DMND304)

• Drug Name: Miltefosine
• Synonyms: HDPC; HePC; Hexadecylphosphocholine; Hexadecylphosphorylcholine; Impavido; Miltefosina; Miltefosinum; Miltex; Baxter Oncology brand of miltefosine; Baxter brand of miltefosine; Miltefosin C; Prasfarma brand of miltefosine; D 18506; IN1227; D-18506; H-1850; M-7200; Miltefosina [INN-Spanish]; Miltefosine (INN); Miltefosine[INN:BAN]; Miltefosinum [INN-Latin]; N-Hexadecylphosphorylcholine; TF-002; Choline hydroxide, hexadecyl hydrogen phosphate, inner salt; Choline, hexadecyl hydrogen phosphate, inner salt; Hexadecyl 2-(trimethylazaniumyl)ethyl phosphate; Choline phosphate, hexadecyl ester, hydroxide, inner salt; Choline phosphate, hexadecyl ester, hydroxide, inner salt (6CI); Hexadecyl 2-(trimethyl-.lambda.~5~-azanyl)ethyl hydrogen phosphate; Ethanaminium, 2-(((hexadecyloxy)hydroxyphosphinyl)oxy)-N,N,N-trimethyl-, hydroxide, inner salt; Ethanaminium, 2-(((hexadecyloxy)hydroxyphosphinyl)oxy)-N,N,N-trimethyl-, hydroxide, innner salt; 1-Hexadecylphosphorylcholine; 2-(((Hexadecyloxy)hydroxyphosphinyl)oxy)-N,N,N-trimethylethanaminium hydroxide, inner salt; 3,5-Dioxa-4-phosphaunacosan-1-aminium, 4-hydroxy-N,N,N-trimethyl-, hydroxide, inner salt, 4-oxide

Indication

Disease Entry	ICD 11	Status	REF
Chronic urticaria	N.A.	Approved	[1]
Leishmaniasis	1F54	Approved	[2]
Visceral leishmaniasis	1F54.0	Phase 2	[3]

• Therapeutic Class: Antifungal Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 407.6
  Logarithm of the Partition Coefficient (xlogp); 6.7
  Rotatable Bond Count (rotbonds); 20
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Half-life: The concentration or amount of drug in body reduced by one-half in 7.05 days [4]
  Metabolism: The drug is metabolized via phospholipase D, releasing choline, choline-containing metabolites, and hexadecanol []
• Chemical Identifiers:
  Formula: C21H46NO4P
  IUPAC Name: hexadecyl 2-(trimethylazaniumyl)ethyl phosphate
  Canonical SMILES: CCCCCCCCCCCCCCCCOP(=O)([O-])OCC[N+](C)(C)C
  InChI: InChI=1S/C21H46NO4P/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-20-25-27(23,24)26-21-19-22(2,3)4/h5-21H2,1-4H3
  InChIKey: PQLXHQMOHUQAKB-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3599
  ChEBI ID: CHEBI:75283
  CAS Number: 58066-85-6
  DrugBank ID: DB09031
  TTD ID: D00FGR
  INTEDE ID: DR1092
  ACDINA ID: D00436
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phospholipase A2 (PLA2G1B)	TT9V5JH	PA21B_HUMAN	Inhibitor	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Choline phosphatase 1 (PLD1) Main DME	DEB2ZMT	PLD1_HUMAN	Substrate	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Drug Response	[6]
Protein kinase C alpha type (PRKCA)	OT5UWNRD	KPCA_HUMAN	Post-Translational Modifications	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Chronic urticaria

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Phospholipase A2 (PLA2G1B)	DTT	PLA2G1B	2.65E-01	-0.08	-0.21
Choline phosphatase 1 (PLD1)	DME	PLD1	5.04E-04	6.65E-01	1.71E+00

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Miltefosine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Levonorgestrel	DM1DP7T	Moderate	Altered absorption of Miltefosine caused by Levonorgestrel.	Contraceptive management [QA21]	[8]
Oestradiol valerate and dienogest	DMZK0FQ	Moderate	Altered absorption of Miltefosine caused by Oestradiol valerate and dienogest.	Endometriosis [GA10]	[9]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Eisenoxyd	E00585	56841934	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Miltefosine 50 mg capsule	50 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Miltefosine FDA Label
• [2] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [3] Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005-2009). Rev Iberoam Micol. 2009 Mar 31;26(1):15-22.
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg. 2006 Dec;100 Suppl 1:S17-20.
• [6] MDR1 causes resistance to the antitumour drug miltefosine. Br J Cancer. 2001 May 18;84(10):1405-11. doi: 10.1054/bjoc.2001.1776.
• [7] Dimethylsphingosine and miltefosine induce apoptosis in lung adenocarcinoma A549?cells in a synergistic manner. Chem Biol Interact. 2019 Sep 1;310:108731. doi: 10.1016/j.cbi.2019.108731. Epub 2019 Jun 29.
• [8] Product Information. Impavido (miltefosine). Paladin Therapeutics Inc, Wilmington, DE.
• [9] Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8. [PMID: 8162660]