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- Friberg Hietala, Sofia, 1973, et al.
(författare)
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Population pharmacokinetics of amodiaquine and desethylamodiaquine in pediatric patients with uncomplicated falciparum malaria
- 2007
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Ingår i: JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 12, s. 222-222
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Tidskriftsartikel (refereegranskat)abstract
- The study aimed to characterize the population pharmacokinetics of amodiaquine (AQ) and its major metabolite N-desethylamodiaquine (N-DEAQ), and to assess the correlation between exposure to N-DEAQ and treatment outcome. Blood samples from children in two studies in Zanzibar and one in Papua New Guinea were included in the pharmacokinetic analysis (n = 86). The children had been treated with AQ in combination with artesunate or sulphadoxine-pyrimethamine. The population pharmacokinetics of AQ and N-DEAQ were modeled using the non-linear mixed effects approach as implemented in NONMEM. Bayesian post-hoc estimates of individual pharmacokinetic parameters were used to generate individual profiles of N-DEAQ exposure. The correlation between N-DEAQ exposure and effect was studied in 212 patients and modeled with logistic regression in NONMEM. The pharmacokinetics of AQ and N-DEAQ were best described by two parallel two-compartment models with a central and a peripheral compartment for each compound. The systemic exposure to AQ was low in comparison to N-DEAQ. The t (1/2lambda) of N-DEAQ ranged from 3 days to 12 days. There was a statistically significant, yet weak, association between N-DEAQ concentration on day 7 and treatment outcome. The age-based dosing schedule currently recommended in Zanzibar appeared to result in inadequate exposure to N-DEAQ in many patients.
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| 2. |
- Msellem, Mwinyi I
(författare)
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Efficacy of artemisinin based combination therapy and effectiveness of rapid diagnostic test for management of patients with plasmodium falciparum malaria in Zanzibar
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Due to rapid spread of antimalarial drug resistance to Plasmodium falciparum malaria many African countries have recently changed their first-line treatment policy to artemisinin-based combination therapy (ACT). Zanzibar was one of the first regions in Africa to implement ACT free of charge to all age groups through public health facilities in 2003. The introduction of ACT, a highly efficacious but also considerably more expensive treatment than previously used mono-therapies, puts a heavy extra burden on malaria control programmes in Africa. This highlights the need of improved diagnostics to ensure targeting of ACT to patients with parasitologically confirmed malaria infection, particularly in settings beyond the reach of high quality microscopy service. Rapid diagnostic tests (RDT) for malaria represent such a potential candidate, considering they are simple to use and do not require highly trained staff, advanced laboratory facilities or electricity. The aim of this thesis was to study the efficacy of ACT in children with uncomplicated P. falciparum malaria and the effectiveness of RDT for management of fever patients in rural health facilities in Zanzibar. The studies included in the thesis are a part of the scientific evaluation of the ongoing integrated, wide scale, high coverage malaria control interventions in Zanzibar. Methods: Study I was a comparative clinical trial assessing the efficacy of artesunate+amodiaquine (ASAQ) and artemether-lumefantrine (AL) in children with microscopically confirmed uncomplicated P. falciparum malaria. Some 408 patients were enrolled in this study, which was conducted between November 2002 and February 2003 in Kivunge and Micheweni Cottage Hospitals, i.e. prior to the of deployment of the drugs as first- and second line treatment for uncomplicated malaria in Zanzibar. Follow-up was extended to 42 days. Primary end-point was polymerase chain reaction (PCR) adjusted cure rates by day 42 in the respective treatment arms. Study II was a cross-over validation study assessing the influence of RDT aided diagnosis on ACT prescription compared to clinical diagnosis (CD) only in patients with fever within the last 48 hours attending 4 primary health care facilities in Zanzibar. Some 1887 patients were enrolled between February and August 2005. Follow-up was 14 days. ACT was to be prescribed to patients diagnosed with malaria in both groups. Results: Study I. PCR adjusted cure rates by day 42 were 188/206 (91%) for ASAQ and 185/197 (94%) for AL, [Odds ratio (OR) 1.48 95% CI 0.69-3.15; p=0.314]. However, AL provided a stronger protection against reinfections during follow-up. Study II. RDT was associated with lower prescription rate of ACT than CD alone, 361/1005 (36%) compared with 752/882 (85%) [OR 0.04 (95%CI 0.03-0.05) p<0.001]. In contrast, prescription of antibiotics was higher after RDT than CD alone, i.e. 372/1005 (37%) and 235/882 (27%) [OR 1.8 (95%CI 1.5-2.2) p<0.001]. Conclusion: Both ASAQ and AL were highly efficacious, which justify their introduction as new malaria treatment policy in Zanzibar. RDTs resulted in improved adequate treatment and may therefore represent an important tool for management of patients with fever in peripheral health care settings in Zanzibar.
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