Rimantadine
Rimantadine is an M2 ion channel inhibitor which specifically inhibits the replication of influenza A viruses by interfering with the uncoating process of the virus. M2 inhibitors block the ion channel formed by the M2 protein that spans the viral membrane (Hay 1985, Sugrue 1991). The influenza virus enters its host cell by receptor-mediated endocytosis. Thereafter, acidification of the endocytotic vesicles is required for the dissociation of the M1 protein from the ribonucleoprotein complexes. Only then are the ribonucleoprotein particles imported into the nucleus via the nuclear pores. The hydrogen ions needed for acidification pass through the M2 channel. Rimantadine blocks the channel (Bui 1996).
The drug is effective against all influenza A subtypes that have previously caused disease in humans (H1N1, H2N2 and H3N2), but not against influenza B virus, because the M2 protein is unique to influenza A viruses. Rimantadine is not active against the avian flu subtype H5N1 strains that have recently caused disease in humans (Li 2004).
For both the prevention and treatment of influenza A, rimantadine has a comparable efficacy to amantadine but a lower potential for causing adverse effects (Stephenson 2001, Jefferson 2004).
The development of neutralising antibodies to influenza strains seems not to be affected by rimantadine. However, the presence of IgA in nasal secretions was significantly diminished in one study (Clover 1991).
A recently published study revealed an alarming increase in the incidence of amantadine-resistant and rimantadine-resistant H3N2 influenza A viruses over the past decade. In a recently published study, which assessed more than 7,000 influenza A viruses obtained worldwide from 1994 to 2005, drug resistance against amantadine and rimantadine increased from 0.4 % to 12.3 % (Bright 2005). Viruses collected in 2004 from South Korea, Taiwan, Hong Kong, and China show drug-resistance frequencies of 15 %, 23 %, 70 %, and 74 %, respectively. Some authors have suggested that the use of amantadine and rimantadine should be discouraged (Jefferson 2006). Recently, 109 out of 120 (91 %) of influenza A H3N2 viruses isolated from patients in the US contained an amino acid change at position 31 of the M2 protein, which confers resistance to amantadine and rimantadine. On the basis of these results, the Centre for Disease Control recommended that neither amantadine nor rimantadine be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2005-06 influenza season (CDC 2006).
Rimantadine is an M2 ion channel inhibitor which specifically inhibits the replication of influenza A viruses by interfering with the uncoating process of the virus. M2 inhibitors block the ion channel formed by the M2 protein that spans the viral membrane (Hay 1985, Sugrue 1991). The influenza virus enters its host cell by receptor-mediated endocytosis. Thereafter, acidification of the endocytotic vesicles is required for the dissociation of the M1 protein from the ribonucleoprotein complexes. Only then are the ribonucleoprotein particles imported into the nucleus via the nuclear pores. The hydrogen ions needed for acidification pass through the M2 channel. Rimantadine blocks the channel (Bui 1996).The drug is effective against all influenza A subtypes that have previously caused disease in humans (H1N1, H2N2 and H3N2), but not against influenza B virus, because the M2 protein is unique to influenza A viruses. Rimantadine is not active against the avian flu subtype H5N1 strains that have recently caused disease in humans (Li 2004).
For both the prevention and treatment of influenza A, rimantadine has a comparable efficacy to amantadine but a lower potential for causing adverse effects (Stephenson 2001, Jefferson 2004).
The development of neutralising antibodies to influenza strains seems not to be affected by rimantadine. However, the presence of IgA in nasal secretions was significantly diminished in one study (Clover 1991).
A recently published study revealed an alarming increase in the incidence of amantadine-resistant and rimantadine-resistant H3N2 influenza A viruses over the past decade. In a recently published study, which assessed more than 7,000 influenza A viruses obtained worldwide from 1994 to 2005, drug resistance against amantadine and rimantadine increased from 0.4 % to 12.3 % (Bright 2005). Viruses collected in 2004 from South Korea, Taiwan, Hong Kong, and China show drug-resistance frequencies of 15 %, 23 %, 70 %, and 74 %, respectively. Some authors have suggested that the use of amantadine and rimantadine should be discouraged (Jefferson 2006). Recently, 109 out of 120 (91 %) of influenza A H3N2 viruses isolated from patients in the US contained an amino acid change at position 31 of the M2 protein, which confers resistance to amantadine and rimantadine. On the basis of these results, the Centre for Disease Control recommended that neither amantadine nor rimantadine be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2005-06 influenza season (CDC 2006).
The drug is effective against all influenza A subtypes that have previously caused disease in humans (H1N1, H2N2 and H3N2), but not against influenza B virus, because the M2 protein is unique to influenza A viruses. Rimantadine is not active against the avian flu subtype H5N1 strains that have recently caused disease in humans (Li 2004).
For both the prevention and treatment of influenza A, rimantadine has a comparable efficacy to amantadine but a lower potential for causing adverse effects (Stephenson 2001, Jefferson 2004).
The development of neutralising antibodies to influenza strains seems not to be affected by rimantadine. However, the presence of IgA in nasal secretions was significantly diminished in one study (Clover 1991).
A recently published study revealed an alarming increase in the incidence of amantadine-resistant and rimantadine-resistant H3N2 influenza A viruses over the past decade. In a recently published study, which assessed more than 7,000 influenza A viruses obtained worldwide from 1994 to 2005, drug resistance against amantadine and rimantadine increased from 0.4 % to 12.3 % (Bright 2005). Viruses collected in 2004 from South Korea, Taiwan, Hong Kong, and China show drug-resistance frequencies of 15 %, 23 %, 70 %, and 74 %, respectively. Some authors have suggested that the use of amantadine and rimantadine should be discouraged (Jefferson 2006). Recently, 109 out of 120 (91 %) of influenza A H3N2 viruses isolated from patients in the US contained an amino acid change at position 31 of the M2 protein, which confers resistance to amantadine and rimantadine. On the basis of these results, the Centre for Disease Control recommended that neither amantadine nor rimantadine be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2005-06 influenza season (CDC 2006).
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