U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C43H68ClNO11.H2O
Molecular Weight 828.468
Optical Activity ( - )
Defined Stereocenters 14 / 14
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of PIMECROLIMUS HYDRATE

SMILES

O.[H][C@]12O[C@](O)([C@H](C)C[C@@H]1OC)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O[C@@]([H])([C@H](C)[C@@H](O)CC(=O)[C@H](CC)\C=C(C)\C[C@H](C)C[C@@H]2OC)C(\C)=C\[C@@H]4CC[C@H](Cl)[C@@H](C4)OC

InChI

InChIKey=NZIZEODSJUZSHZ-MNZFELGNSA-N
InChI=1S/C43H68ClNO11.H2O/c1-10-30-18-24(2)17-25(3)19-36(53-8)39-37(54-9)21-27(5)43(51,56-39)40(48)41(49)45-16-12-11-13-32(45)42(50)55-38(28(6)33(46)23-34(30)47)26(4)20-29-14-15-31(44)35(22-29)52-7;/h18,20,25,27-33,35-39,46,51H,10-17,19,21-23H2,1-9H3;1H2/b24-18+,26-20+;/t25-,27+,28+,29-,30+,31-,32-,33-,35+,36-,37-,38+,39+,43+;/m0./s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12113647 https://www.ncbi.nlm.nih.gov/pubmed/12090545

Pimecrolimus, an ascomycin macrolactam derivative, is an inhibitor of T-cell and mast-cell activation, developed and launched by Novartis for the potential treatment of psoriasis and allergic, irritant and atopic dermatitis. The topical formulation had been launched in the US by February 2002 for mild-to-moderate atopic dermatitis in patients aged two years and older. Pimecrolimus is an immunomodulating agent. The mechanism of action of pimecrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known. It has been demonstrated that pimecrolimus binds with high affinity to macrophilin-12 (FKBP-12) and inhibits the calcium dependent phosphatase, calcineurin. Therefore, it inhibits T cell activation by blocking the transcription of early cytokines. In particular, pimecrolimus inhibits at nanomolar concentrations Interleukin-2 and interferon gamma (Th1-type) and Interleukin-4 and Interleukin-10 (Th2-type) cytokine synthesis in human T-cells. In addition, pimecrolimus prevents the release of inflammatory cytokines and mediators from mast cells in vitro after stimulation by antigen/IgE. Following the administration of a single oral radiolabeled dose of pimecrolimus numerous circulating O-demethylation metabolites were seen. Studies with human liver microsomes indicate that pimecrolimus is metabolized in vitro by the CYP3A sub-family of metabolizing enzymes. No evidence of skin mediated drug metabolism was identified in vivo using the minipig or in vitro using stripped human skin.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
ELIDEL

Approved Use

ELIDEL ® (pimecrolimus) Cream 1% is indicated as second-line therapy for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adults and children 2 years of age and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable. ELIDEL Cream is not indicated for use in children less than 2 years of age (see WARNINGS, boxed WARNING, and PRECAUTIONS, Pediatric Use).

Launch Date

2001
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.89 ng/mL
1 % 2 times / day multiple, topical
dose: 1 %
route of administration: Topical
experiment type: MULTIPLE
co-administered:
PIMECROLIMUS blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
43.3 μg/L
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
10.5 μg/L
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
79 μg/L
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
147.5 μg/L
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
18.57 ng × h/mL
1 % 2 times / day multiple, topical
dose: 1 %
route of administration: Topical
experiment type: MULTIPLE
co-administered:
PIMECROLIMUS blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
159 μg × h/L
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
24.4 μg × h/L
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
377 μg × h/L
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
966.1 μg × h/L
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.5 h
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
11.5 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
42.6 h
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
35 h
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PIMECROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.5%
PIMECROLIMUS plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
30 mg 2 times / day steady, oral
Highest studied dose
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
unhealthy, 18 - 40 years
n = 8
Health Status: unhealthy
Condition: psoriasis
Age Group: 18 - 40 years
Sex: M
Population Size: 8
Sources:
60 mg single, oral
Highest studied dose
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources:
healthy, 18 - 40 years
n = 6
Health Status: healthy
Age Group: 18 - 40 years
Sex: M
Population Size: 6
Sources:
1 % 4 times / day steady, topical
Recommended
Dose: 1 %, 4 times / day
Route: topical
Route: steady
Dose: 1 %, 4 times / day
Sources:
unhealthy, 3 months to 81.2 years
n = 947
Health Status: unhealthy
Condition: atopic dermatitis
Age Group: 3 months to 81.2 years
Sex: M+F
Population Size: 947
Sources:
Disc. AE: Hypersensitivity...
AEs leading to
discontinuation/dose reduction:
Hypersensitivity (2.3%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypersensitivity 2.3%
Disc. AE
1 % 4 times / day steady, topical
Recommended
Dose: 1 %, 4 times / day
Route: topical
Route: steady
Dose: 1 %, 4 times / day
Sources:
unhealthy, 3 months to 81.2 years
n = 947
Health Status: unhealthy
Condition: atopic dermatitis
Age Group: 3 months to 81.2 years
Sex: M+F
Population Size: 947
Sources:
Overview

Overview

Drug as perpetrator​Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

Apply a thin layer of ELIDEL (pimecrolimus) Cream, 1% to the affected skin twice daily.
Route of Administration: Topical
Primary human basophils pre-treated or not with 0.5-50 μMol pimecrolimus were exposed to various concentrations of recombinant Bet v 1a allergen, bee or wasp venom extracts and anti-IgE for 20 min, and then examined for the expression of CD45, CD193, CD203c, CD63 and CD164 using flow cytometry. The inhibition was concentration-dependent; approximately half of the basophils were inhibited in the presence of 2.5 mMol pimecrolimus.
Name Type Language
PIMECROLIMUS HYDRATE
Common Name English
15,19-EPOXY-3H-PYRIDO(2,1-C)(1,4)OXAAZACYCLOTRICOSINE-1,7,20,21(4H,23H)-TETRONE, 3-((1E)-2-((1R,3R,4S)-4-CHLORO-3-METHOXYCYCLOHEXYL)-1-METHYLETHENYL)-8-ETHYL-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26A-HEXADECAHYDRO-5,19-DIHYDROXY-14,16-DIMETHOXY-4,10,
Systematic Name English
Code System Code Type Description
SMS_ID
100000174203
Created by admin on Sat Dec 16 19:08:19 GMT 2023 , Edited by admin on Sat Dec 16 19:08:19 GMT 2023
PRIMARY
CAS
1000802-56-1
Created by admin on Sat Dec 16 19:08:19 GMT 2023 , Edited by admin on Sat Dec 16 19:08:19 GMT 2023
PRIMARY
FDA UNII
89GTE436P6
Created by admin on Sat Dec 16 19:08:19 GMT 2023 , Edited by admin on Sat Dec 16 19:08:19 GMT 2023
PRIMARY
PUBCHEM
91886159
Created by admin on Sat Dec 16 19:08:19 GMT 2023 , Edited by admin on Sat Dec 16 19:08:19 GMT 2023
PRIMARY