Indication:
Herpes zoster
Herpes simplex
Summary-
Inosiplex is a new immunomodulating agent.
Preliminary data indicate that the compound may improve the immunological status of some pre-AIDS patients and may delay progression of pre-AIDS to AIDS.
Inosiplex could prsumbly long term in the patients, since it is administered orally and has
not been associated with side effects. However more extensive are needed to establish
the safety and efficacy of the agent.
NewPort Pharmaceuticals submitted a New Drug application (NDA) September 3, 1985,
requesting approval of Inosiplex (Isoprinosine) for immunorestoration in pre-AIDS patients,
but was rejected by the FDA in February 1986
Adverse Reaction:
Side effects-
In clinical studies no serious side effects were reported after continous inosoplex
administration for 1 week to 7 years at doses of 1 to 8g/day.
Occasional trasnsit nausea was associated with the ingestion of large number of tablets,
a transcient rise in serum and uric acid related to the metabolism of the drug, occured in
a small number of patients.
Initiate concomittant administration of drugs that increase uric acid levels with caution,
since potential for additive effects has not been studied
Pharmacology/ Pharmacokinetics:
Pharmacology-
Inosiplex (inosine pranobex, BAN) is a synthetic complex formed from the
p-acetamidobenzoic acid salt of N-N dimethylamino-2-propranol and inosine in a 3:1
molar ratio.
Early studies examined inosiplex as an antiviral agent. however the recent research has
focussed on its immunomudalating properties and suggess that its antiviral activity
involves enhancement of host defences rather than direct inhibition of viral replication
Inosiplex may be more appropiately classed with those agents that regulate immunity
eg.levamisole
Inosiplex auguments immunological events triggered by such mitogens, antigens,phagocyte
stimulants or lymphokines. Inosiplex lone does not appear to affect lymphocytes or
macrophages. In the presence of triggering agents, it results in an increase in mitogen
responses
Exactly how the drug acts on lymphocytes to alter the magnitude of triggered response is
unclear. It may invlove one or several nucleotide levels or calcium ion flux. Inosplex also
potentiates interferon activity through mechansims which remain unclear
Pharmacokinetics-
Inosiplex is rapidly metabolized oral and IV admin . The half- life of the inosine portion of
the parent complex is 3 minutes after IV admin. and 50 minutes after oral admin.
In animal models 90% of the inosine moiety is excrerted in the urine as allantoin and uric
acid, along with small amounts of hypoxanthine, xanthine and adenine
Clinical studies--
Clinical trial examining the use of inosiplex in a variety of viral disorders (eg.herpes zoyster,
herpes simplex, rhinovirus, influenza A and subacute sclerosing panencephalitis)
rheumatoid arthiritis and solid tumors have not been able to establish defenite efficacy of
the drug in any of these disorders.
A preliminary study involving four patients with pre-Acquired Immune Deficiency syndrome
(AIDS) complex ( a prodrome of AIDS and five patients with AIDS given 4g isosiplex per day for 4 weeks showed enchancement of mitogen- induced lymphocyte proliferative responses in two patients with the pre-AIDS complex.
These results agreed with the data from invitro study of inosiplexs effect on lymphocytes
from pre-AIDS patients, and patients with AIDS and healthy heterosexual controls which
demonstrated that inosiplex could partially restore some of the depressed lymphocyte
functions associated with AIDS.
After examination of the combined preliminary results of three studies (unpublished data)
Newport Pharmaceuticals reported to FDA officials that there appeared to be trend a
delay in the development of fully developed AIDS in -pre-AIDS patients treated with
inosiplex for 28 days. Amulticenter study is in progress to evaluate the use of inosiplex
in pre-AIDS patients
Manufacturer Details