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Details

Stereochemistry ABSOLUTE
Molecular Formula C43H68ClNO11
Molecular Weight 810.4547
Optical Activity UNSPECIFIED
Defined Stereocenters 14 / 14
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of PIMECROLIMUS

SMILES

CC[C@]1([H])/C(/[H])=C(\C)/C[C@]([H])(C)C[C@@]([H])([C@]2([H])[C@]([H])(C[C@@]([H])(C)[C@@](C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O[C@]([H])(/C(=C(\[H])/[C@]4([H])CC[C@@]([H])([C@@]([H])(C4)OC)Cl)/C)[C@]([H])(C)[C@]([H])(CC1=O)O)(O)O2)OC)OC

InChI

InChIKey=KASDHRXLYQOAKZ-XDSKOBMDSA-N
InChI=1S/C43H68ClNO11/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/b24-18+,26-20+/t25-,27+,28+,29-,30+,31-,32-,33-,35+,36-,37-,38+,39+,43+/m0/s1

HIDE SMILES / InChI

Molecular Formula C43H68ClNO11
Molecular Weight 810.4547
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 14 / 14
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
Curator's Comment:: 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

1008201600000
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
Health Status: unhealthy
Age Group: 18 - 40 years
Sex: M
Sources:
60 mg single, oral
Highest studied dose
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources:
healthy, 18 - 40 years
Health Status: healthy
Age Group: 18 - 40 years
Sex: M
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
Health Status: unhealthy
Age Group: 3 months to 81.2 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 3 months to 81.2 years
Sex: M+F
Sources:
Overview

Overview

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Ascomycin macrolactam derivative SDZ ASM 981 inhibits the release of granule-associated mediators and of newly synthesized cytokines in RBL 2H3 mast cells in an immunophilin-dependent manner.
1998 Sep
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.
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:55:39 UTC 2021
Edited
by admin
on Sat Jun 26 09:55:39 UTC 2021
Record UNII
7KYV510875
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PIMECROLIMUS
INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
ELIDEL
Brand Name English
PIMECROLIMUS [MI]
Common Name English
PIMECROLIMUS [JAN]
Common Name English
PIMECROLIMUS [INN]
Common Name English
SDZ ASM-981
Code English
SDZ ASM 981
Code English
PIMECROLIMUS [WHO-DD]
Common Name English
PIMECROLIMUS [ORANGE BOOK]
Common Name English
PIMECROLIMUS [MART.]
Common Name English
PIMECROLIMUS [USAN]
Common Name English
SDZ-ASM-981
Code English
SDZ-ASM 981
Code English
PIMECROLIMUS [VANDF]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C146638
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
NDF-RT N0000175458
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
WHO-VATC QD11AH02
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
NDF-RT N0000175457
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
WHO-ATC D11AH02
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
Code System Code Type Description
INN
7632
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
LACTMED
Pimecrolimus
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
FDA UNII
7KYV510875
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
RXCUI
321952
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY RxNorm
EPA CompTox
137071-32-0
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
EVMPD
SUB16457MIG
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
DRUG CENTRAL
2168
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
CAS
137071-32-0
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
ChEMBL
CHEMBL1200686
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
PUBCHEM
6509979
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
WIKIPEDIA
PIMECROLIMUS
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
MERCK INDEX
M8811
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C47671
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
DRUG BANK
DB00337
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
MESH
C117268
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
IUPHAR
6783
Created by admin on Sat Jun 26 09:55:39 UTC 2021 , Edited by admin on Sat Jun 26 09:55:39 UTC 2021
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
Based on the results of the aforementioned radiolabeled study, following a single oral dose of pimecrolimus ~81% of the administered radioactivity was recovered, primarily in the feces (78.4%) as metabolites. Less than 1% of the radioactivity found in the feces was due to unchanged pimecrolimus.
FECAL
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC