Identification

Summary

Lutropin alfa is a form of recombinant human luteinizing hormone used to treat female infertility due to hypothalamic or pituitary insufficiency, or due to profound luteinizing hormone deficiency.

Brand Names
Luveris, Pergoveris
Generic Name
Lutropin alfa
DrugBank Accession Number
DB00044
Background

Lutropin alfa is a recombinant human luteinizing hormone produced in yeast with 2 subunits, alpha = 92 residues, beta = 121 residues. It is a heterodimeric glycoprotein made up of monomeric units. Lutropin alfa was the first and only recombinant human form of luteinizing hormone (LH) developed for use in the stimulation of follicular development. Its pharmacological action mimics the biological activity of endogenous LH; an acute rise of LH, or LH surge, in females triggers ovulation and the development of the corpous luteum. In males, LH stimulates Leydig cell to produce testosterone.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Hormones
Protein Structure
Db00044
Protein Chemical Formula
C1014H1609N287O294S27
Protein Average Weight
30000.0 Da
Sequences
>Alpha Chain
APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCC
VAKSYNRVTVMGGFKVENHTACHCSTCYYHKS
>Beta Chain (LH)
SREPLRPWCHPINAILAVEKEGCPVCITVNTTICAGYCPTMMRVLQAVLPPLPQVVCTYR
DVRFESIRLPGCPRGVDPVVSFPVALSCRCGPCRRSTSDCGGPKDHPLTCDHPQLSGLLF
L
Download FASTA Format
Synonyms
  • Lutropin alfa
  • Lutropin alpha
  • Lutropina alfa

Pharmacology

Indication

For treatment of infertility in women with hypothalamic or pituitary insufficiency (hypogonadotropic hypogonadism) and profound LH deficiency (LH <1.2 international units [IU]/L)

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Used to facilitate female conception, lutropin alfa performs the same actions as luteinizing hormone (LH), which is normally produced in the pituitary gland. Lutropin is usually given in combination with follitropin alfa. Together they stimulate the development of a follicle to prepare the reproductive tract for implementation and pregnancy. Lutropin alfa also stimulates the theca cells to produce androgens and the secretion of estradiol by the follicles. Lutropin alfa and follitropin alfa are discontinued once ultrasound assessment and serum estradiol concentrations show sufficient follicular maturation. hCG is then administered to complete follicular maturation and induce ovulation. In females, a LH surge about halfway through the menstrual cycle triggers the onset of ovulation. Lutropin alfa substitutes for endogenous LH and induces rupture of the preovulatory ovarian follicle and oocyte expulsion. Lutropin alfa induces and maintains the corpus luteum, which then secretes progesterone.

Mechanism of action

Luteinizing hormone binds to a receptor shared with the human chorionic gonadotropin hormone (hCG) on the ovarian theca (and granulosa) cells and testicular Leydig cells. This LH/CG transmembrane receptor is a member of the super-family of G protein-coupled receptors. Adenylate cyclase then activates many other pathways leading to steroid hormone production and other follicle maturation processes.

TargetActionsOrganism
ALutropin-choriogonadotropic hormone receptor
agonist
Humans
Absorption

Mean absolute bioavailability is 56%, following sub-Q administration, maximum serum concentrations reached after 4–16 hours. Time to peak, serum: 9 hours

Volume of distribution

The steady state volume of distribution is around 10-14 L.

Protein binding

Not Available

Metabolism

<5% of dose excreted renally as unchanged drug.

Route of elimination

Total body clearance is approximately 2 to 3 L/h with less than 5 percent of the dose being excreted unchanged renally.

Half-life

Biphasic; terminal half-life is approximately 18 hours.

Clearance
  • 2 – 3 L/h [healthy female following subcutaneous administration]
Adverse Effects
Adverseeffects
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Toxicity

Lutropin alfa is not indicated for people under 16 and over 60, pregnant and lactating women, patients with uncontrolled thyroid and adrenal failure, patients with active, untreated tumours of the hypothalamus and pituitary gland, and in any patient with a condition that makes a normal pregnancy possible such as primary ovarian failure or fibroid tumors of the uterus.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
No interactions found.
Food Interactions
No interactions found.

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LuverisKit82.5 [iU]/1mLSubcutaneousEmd Serono2004-10-082014-11-30US flag
LuverisInjection, powder, for solution75 IUSubcutaneousMerck Europe B.V.2021-02-11Not applicableEU flag
LuverisSolution450 unit / 0.72 mLSubcutaneousEmd Serono, A Division Of Emd Inc., CanadaNot applicableNot applicableCanada flag
LuverisInjection, powder, for solution75 IUSubcutaneousMerck Europe B.V.2021-02-11Not applicableEU flag
LuverisInjection, powder, for solution75 IUSubcutaneousMerck Europe B.V.2021-02-11Not applicableEU flag
LuverisPowder, for solution75 unit / vialSubcutaneousEmd Serono, A Division Of Emd Inc., Canada2005-06-28Not applicableCanada flag
LuverisInjection, powder, for solution75 IUSubcutaneousMerck Europe B.V.2021-02-11Not applicableEU flag
LuverisInjection, powder, for solution75 IUSubcutaneousMerck Europe B.V.2021-02-11Not applicableEU flag
LuverisInjection, powder, for solution75 IUSubcutaneousMerck Europe B.V.2021-02-11Not applicableEU flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
PergoverisLutropin alfa (150 IU) + Follitropin (300 IU)Injection, solutionSubcutaneousMerck Europe B.V.2020-12-21Not applicableEU flag
PergoverisLutropin alfa (75 IU) + Follitropin (150 IU)Injection, powder, for solutionSubcutaneousMerck Europe B.V.2016-09-20Not applicableEU flag
PergoverisLutropin alfa (450 IU) + Follitropin (900 IU)Injection, solutionSubcutaneousMerck Europe B.V.2020-12-21Not applicableEU flag
PergoverisLutropin alfa (150 unit / 0.48 mL) + Follitropin (300 unit / 0.48 mL)SolutionSubcutaneousEmd Serono, A Division Of Emd Inc., CanadaNot applicableNot applicableCanada flag
PergoverisLutropin alfa (75 IU) + Follitropin (150 IU)Injection, powder, for solutionSubcutaneousMerck Europe B.V.2016-09-20Not applicableEU flag
PergoverisLutropin alfa (450 unit / 1.44 mL) + Follitropin (900 unit / 1.44 mL)SolutionSubcutaneousEmd Serono, A Division Of Emd Inc., CanadaNot applicableNot applicableCanada flag
PergoverisLutropin alfa (225 IU) + Follitropin (450 IU)Injection, solutionSubcutaneousMerck Europe B.V.2020-12-21Not applicableEU flag
PergoverisLutropin alfa (75 unit / vial) + Follitropin (150 unit / vial)Kit; Powder, for solutionSubcutaneousEmd Serono, A Division Of Emd Inc., Canada2015-10-22Not applicableCanada flag
PergoverisLutropin alfa (75 IU) + Follitropin (150 IU)Injection, powder, for solutionSubcutaneousMerck Europe B.V.2016-09-20Not applicableEU flag
PergoverisLutropin alfa (225 unit / 0.72 mL) + Follitropin (450 unit / 0.72 mL)SolutionSubcutaneousEmd Serono, A Division Of Emd Inc., CanadaNot applicableNot applicableCanada flag

Categories

ATC Codes
G03GA07 — Lutropin alfa
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
3JGY52XJNA
CAS number
152923-57-4

References

General References
  1. Blanchard J: Gastrointestinal absorption. I. Mechanisms. Am J Pharm Sci Support Public Health. 1975 Sep-Oct;147(5):135-46. [Article]
  2. Louvet JP, Harman SM, Ross GT: Effects of human chorionic gonadotropin, human interstitial cell stimulating hormone and human follicle-stimulating hormone on ovarian weights in estrogen-primed hypophysectomized immature female rats. Endocrinology. 1975 May;96(5):1179-86. [Article]
  3. Nielsen MS, Barton SD, Hatasaka HH, Stanford JB: Comparison of several one-step home urinary luteinizing hormone detection test kits to OvuQuick. Fertil Steril. 2001 Aug;76(2):384-7. [Article]
  4. Gibreel A, Bhattacharya S: Recombinant follitropin alfa/lutropin alfa in fertility treatment. Biologics. 2010 Feb 4;4:5-17. [Article]
  5. Dhillon S, Keating GM: Lutropin alfa. Drugs. 2008;68(11):1529-40. [Article]
UniProt
P01229
Genbank
X00264
PubChem Substance
46507624
RxNav
388084
ChEMBL
CHEMBL1201419
Therapeutic Targets Database
DAP001103
PharmGKB
PA164750539
Drugs.com
Drugs.com Drug Page
Wikipedia
Luteinizing_hormone
FDA label
Download (218 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionInfertility1
4CompletedTreatmentFemale Infertility1
4CompletedTreatmentIn Vitro Fertilization (IVF) / Infertility1
4CompletedTreatmentInfertility2
4CompletedTreatmentInfertility / Progesterone Levels1
4TerminatedTreatmentHyperprolactinemia / Hypothalamic Amenorrhea / Infertility1
4TerminatedTreatmentIdiopathic Hypogonadotropic Hypogonadism1
4Unknown StatusTreatmentFemale Infertility1
4Unknown StatusTreatmentFemale Infertility / In Vitro Fertilisation / Ovarian Stimulation1
4Unknown StatusTreatmentInfertility1

Pharmacoeconomics

Manufacturers
  • Emd serono inc
Packagers
  • EMD Canada Inc.
  • Merck Serono SPA
Dosage Forms
FormRouteStrength
Injection, powder, for solutionParenteral; Subcutaneous75 IU/ML
Injection, solutionSubcutaneous450 UI
KitSubcutaneous82.5 [iU]/1mL
Powder, for solutionSubcutaneous75 unit / vial
SolutionSubcutaneous450 unit / 0.72 mL
Injection, powder, for solution75 iu/1vial
Injection, powder, lyophilized, for solutionSubcutaneous
Injection, powder, for solutionSubcutaneous75 iu
Injection, powder, for solutionSubcutaneous
Kit; powder, for solutionSubcutaneous
PowderParenteral; Subcutaneous
SolutionSubcutaneous
InjectionSubcutaneous
Injection, powder, for solutionSubcutaneous150 IU
Injection, solutionSubcutaneous
Prices
Unit descriptionCostUnit
Luveris 75 unit vial38.88USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5767251No1998-06-162015-06-16US flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)55 °CForastieri, H., Ingham, K.C. J. Biol. Chem. 257:7976-7981 (1982)
hydrophobicity-0.063Not Available
isoelectric point8.44Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Luteinizing hormone receptor activity
Specific Function
Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Gene Name
LHCGR
Uniprot ID
P22888
Uniprot Name
Lutropin-choriogonadotropic hormone receptor
Molecular Weight
78642.01 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Gibreel A, Bhattacharya S: Recombinant follitropin alfa/lutropin alfa in fertility treatment. Biologics. 2010 Feb 4;4:5-17. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 26, 2021 21:13