Gusperimus
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Gusperimus
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| Systematic (IUPAC) name | |
| 1-Amino-19-guanidino-11-hydroxy-4,9,12-triazanonadecane-10,13-dione | |
| Identifiers | |
| CAS number | |
| ATC code | L04 |
| PubChem | |
| Chemical data | |
| Formula | C17H40Cl3N7O3 |
| Mol. mass | 496.903 |
| Pharmacokinetic data | |
| Bioavailability | 100% (i.v. application) |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status |
Rx-only (available only as orphan drug and for clinical studies) |
| Routes | i.v. infusion in isotonic NaCl or s.c. injection |
Contents |
[edit] Chemical Designation
Common references are:
- (+-)-15-Dexyspergualin,
- 1-Amino-19-guanidino-11-hydroxy-4,9,12-triazanonadecane-10,13-dione,
- 15-Deoxyspergualin,
- 15-Deoxyspergualin Hydrochloride,
- 7-{(Aminoiminomethyl)amino]-N-[2-[[4-[(3-aminopropyl)amino]butyl]amino]-
1-hydroxy-2-oxoethyl]heptanamide, - Gusperimus (Trihydrochloride),
- N-[[[4-[(3-Aminopropyl)amino]-butyl]carbamoyl]hydroxymethyl]-
7-guanidinoheptanamide, - Spanidin
[edit] Basic Pharmacological Information
Gusperimus is a derivative of the antitumor antibiotic spergualin with immunosuppressant activity. It inhibits the interleukin-2-stimulated maturation of T cells to the S and G2/M phases and the polarization of the T cells into IFN-gamma-secreting Th1 effector T cells, resulting in the inhibition of growth of activated naive CD4 T cells.
There is little information about the pharmacokinetic properties of gusperimus.
Gusperimus was invented in the laboratories of Squibb-Mayer. Currently, it is manufactured and sponsored for use as orphan drug (see below) and for clinical studies by the Japanese company Euro Nippon Kayaku. The patent claim (see quotation) is that gusperimus may be useful for a variety of hyperreactive inflammatory diseases such as autoimmune diseases. The drug is available in vials containing 100mg each.
[edit] Orphan Drug Indications in Europe
The European Commission has assigned orphan drug status to gusperimus in 2001 for the treatment of Wegener's granulomatosis, a serious condition associated with permanent disability and/or frequent fatal outcome. There have been cases of most ill patients resistant to all forms of usual treatment responding very well to gusperimus.
[edit] Other possible Indications
It has been proposed that gusperimus may benefit patients with the serious neurological disease ALS (Amyotrophic lateral sclerosis). ALS causes permanent motoric deficits and disabilities up to the point that almost all motor functions including breathing and bladder control are lost. The patients have normally no intellectual impairments. Currently, there are no results from controlled studies in ALS patients.
There have been as well positive and negative anedoctal reports in patients with Multiple Sclerosis. There are no sufficient studies in MS patients, too.
The substance may possibly have a use in more common diseases and conditions such as Primary Chronic Polyarthritis (PCP), Morbus Crohn, Lupus erythematodes, the prophylaxis and therapy of transplant rejection or graft versus host disease.
[edit] Side-Effects
Currently, there is only provisional and preliminary data about side-effects available. The following side-effects have been noticed so far:
- Dysgeusia (=abnormal or bad taste)
- Drug induced leukopenia (very common)
- Significant infections related to therapy.
Currently, it is not known, if therapy with gusperimus may increase the risk of malignant diseases (lymphoma, leukemia, solid tumors) as is the case with other highly potent immunosuppressant agents like cyclosporine or tacrolimus.
[edit] Interactions
There has been little experience about clinically relevant interactions. These might be:
- Other immunosuppressant drugs : Risk of infections increased.
- Myelotoxic drugs like 6-Mercaptopurin : Risk of serious bone marrow damage increased.
- Certain NSAIDs : Increased risk of hepatotoxic reactions.
[edit] Dosage
Gusperimus is used in therapeutic cycles. The daily dose and the length of each cycle as well as the length of the treatment free interval depend on the degree of leukopenia/neutropenia caused by gusperimus. It is recommended to obtain complete WBC (White Blood Cell) counts during and after each cycle frequently.
