Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

Mechanism of Action
Lariam acts on the asexual intraerythrocytic forms of the human malaria parasites: Plasmodium falciparum, P. vivax, P. malariae and P. ovale.

Lariam is effective against malaria parasites resistant to other antimalarials such as chloroquine, proguanil, pyrimethamine and pyrimethamine-sulfonamide combinations.

Clinical/Efficacy Studies
In a randomised, double-blind study, non-immune travellers received malaria prophylaxis with Lariam (483 subjects) and atovaquoine-proguanil (493 subjects) who visited a malaria-endemic area. Efficacy of chemoprophylaxis was evaluated as a secondary end point. The average duration of travel was ~2.5 weeks, and 79% of subjects travelled to Africa. 1013 subjects were initially randomised to receive Lariam (n = 505) or atovaquone-proguanil (n = 508). Thirty-seven subjects withdrew due to a variety of reasons.
Of the 976 subjects who received ≥ 1 dose of study drug, 966 (99%) completed the trial and 963 completed the 60-day follow-up period and had efficacy information recorded. Although 10 subjects (5 in each study arm) were identified with circumsporozoite antibodies, none of them developed malaria (minimum efficacy for both Lariam and atovaquone-proguanil was 100%). Overall, there were no cases of confirmed malaria in this study (maximum efficacy for both Lariam and atovaquone-proguanil was 100%). Results indicated that Lariam and atovaquone-proguanil are similarly effective for malaria prophylaxis in non-immune travellers (see Table 1).

Table 1.        Estimates of minimum and maximum efficacy for malaria prophylaxis 
Subjects who received
Variable                                             Atovaquone-proguanil                Lariam Subjects with 60-day efficacy data available,                 486                           477 no.
Subjects who developed circumsporozoite                         5                            5 antibodies, no.
Subjects with confirmed malaria, no.                            0                            0 Minimum efficacy, % (95% Cl)a                             100 (48-100)                100 (48-100) Maximum efficacy, % (95% Cl)b                             100 (99-100)                100 (99-100) a
Minimum efficacy = 100 x [1 – (no. of subjects with confirmed malaria/no. with circumsporozoite antibodies)] b
Maximum efficacy = 100 x [1 – (no. of subjects with confirmed malaria/no. with 60-day efficacy data)] 

Pharmacokinetic Properties