79217-60-0 Usage
Application in Particular Diseases
In Rheumatic Arthritis:
Cyclosporine reduces production of cytokines involved in T-cell activation and has direct effects on B cells, macrophages, bone, and cartilage cells. Its onset appears to be 1 to 3 months. Important toxicities at doses of 1 to 10 mg/kg/day include hypertension, hyperglycemia, nephrotoxicity, tremor, GI intolerance, hirsutism, and gingival hyperplasia. Cyclosporine should be reserved for patients refractory to or intolerant of other DMARDs. It should be avoided in patients with current or past malignancy, uncontrolled hypertension, renal dysfunction, immunodeficiency, low white blood cell or platelet counts, or elevated liver function tests.
Description
Cyclosporine is a cyclic polypeptide with potent, partially selective immunosupressive
activity. Isolated from the species Cylindrocarpon lucidium and
Trichoderma polysporum, cyclosporine is useful in the prevention and treatment
of graft/host disease and the prevention of rejection following organ transplantation.
It appears to act by preferentially suppressing T-lymphocytes.
Cyclosporine lacks myelotoxicity, although impaired renal and liver function have
been observed. Initial administration is via the intravenous route, followed by
oral maintenance therapy.
Originator
Sandoz (Switzerland)
Indications
Cyclosporine (Sandimmune) is a potent inhibitor of antibody-
and cell-mediated immune responses and is the
immunosuppressant of choice for the prevention of
transplant rejection. It also has application in the treatment
of autoimmune diseases.
Cyclosporine is a highly stable 11-amino acid cyclic
polypeptide. The molecule is very lipophilic and essentially
is not soluble in water. It can be administered intravenously,
orally, or by injection.
Brand name
SANDIMMUN
Mechanism of action
Cyclosporine can bind to the cytosolic protein cytophilin
C. This drug–protein complex inhibits calcineurin
phosphatase activity, which leads to a decreased
synthesis and release of several cytokines,
including interleukins IL-2, IL-3, IL-4, interferon-, and
tumor necrosis factor.
Cyclosporine exhibits a high degree of specificity in
its actions on T cells without significantly impairing Bcell
activity. It can inhibit the T cell–dependent limb of
antibody production by lymphocytes by preventing the
differentiation of B cells into antibody-secreting plasma
cells. Because T cells appear to require IL-2 stimulation
for their continuous growth, cyclosporine impairs the
proliferative response of T cells to antigens. However,
once T cells have been stimulated by antigens to synthesize
IL-2, cyclosporine cannot suppress the proliferation
of T cells induced by this cytokine.
Pharmacology
After oral administration, cyclosporine is absorbed
slowly and incompletely, with great variation among individuals.
Peak plasma concentrations are reached in
3 to 4 hours, and the plasma half-life is 10 to 27 hours.
The drug is extensively metabolized by hepatic mixedfunction
oxidase enzymes and is excreted principally via
the bile into the feces. Metabolism results in inactivation
of the immunosuppressive activity.Agents that enhance
or inhibit the mixed-function oxidase enzymes
will alter the therapeutic response to cyclosporine.
Clinical Use
Cyclosporine has been approved for use in allogeneic
kidney, liver, and heart transplant patients and is under
study for use in pancreas, bone marrow, single lung, and
heart–lung transplant procedures. It is recommended
that corticosteroids, such as prednisone, be used concomitantly,
although at half or less of their usual dose.
Such combined therapy leads to fewer side effects, a decreased
incidence of infectious complications, efficacy
of lower doses of cyclosporine, and a better history of
patient survival.
Cyclosporine appears to have promise in the treatment
of autoimmune diseases. It has a beneficial effect
on the course of rheumatoid arthritis, uveitis, insulindependent
diabetes, systemic lupus erythematosus, and
psoriatic arthropathies in some patients. Toxicity is
more of a problem in these conditions than during use
in transplantation, since higher doses of cyclosporine
are often required to suppress autoimmune disorders.
Side effects
Compared with previously available therapy, the adverse
effects associated with cyclosporine are much less severe
but still worthy of concern. Nephrotoxicity, which can occur
in up to 75% of patients, ranges from severe tubular
necrosis to chronic interstitial nephropathy.This effect is
generally reversible with dosage reduction. Vasoconstriction
appears to be an important aspect of cyclosporine-
induced nephrotoxicity. Hypertension occurs in
25% of the patients and more frequently in patients with
some degree of renal dysfunction; the concomitant use of
antihypertensive drugs may prove useful. Hyperglycemia,
hyperlipidemia, transient liver dysfunction, and
unwanted hair growth are also observed.
Veterinary Drugs and Treatments
Cyclosporine may be useful as an immunosuppressant for immunemediated
diseases
(see dosage section) and as part of a protocol to
reduce the rejection of allografts in transplant medicine in dogs and
cats.
Shipping
UN3249 Medicine, solid, toxic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials.
Check Digit Verification of cas no
The CAS Registry Mumber 79217-60-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,9,2,1 and 7 respectively; the second part has 2 digits, 6 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 79217-60:
(7*7)+(6*9)+(5*2)+(4*1)+(3*7)+(2*6)+(1*0)=150
150 % 10 = 0
So 79217-60-0 is a valid CAS Registry Number.
InChI:InChI=1/C62H111N11O12/c1-25-27-28-40(15)52(75)51-56(79)65-43(26-2)58(81)67(18)33-48(74)68(19)44(29-34(3)4)55(78)66-49(38(11)12)61(84)69(20)45(30-35(5)6)54(77)63-41(16)53(76)64-42(17)57(80)70(21)46(31-36(7)8)59(82)71(22)47(32-37(9)10)60(83)72(23)50(39(13)14)62(85)73(51)24/h25,27,34-47,49-52,75H,26,28-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b27-25+/t40-,41+,42-,43+,44+,45+,46+,47+,49+,50+,51+,52-/m1/s1
