Pharmacodynamic analysis of antimalarials used in Plasmodium falciparum imported malaria in northern Italy.
BACKGROUND
Conventional treatment of imported malaria in Italy consists of quinine or mefloquine. Since beta-arthemeter is now available, an open-label pharmacodynamic analysis was performed in 73 adults with uncomplicated Plasmodium falciparum malaria. In vitro susceptibility to mefloquine and quinine was evaluated at admission.


METHODS
According to clinical status, baseline parasitemia (P(0)), and premunition, the patients received intravenous quinine, oral mefloquine, or beta-arthemeter. The following parameters were measured: parasitemia at 0, 6, 12, and 24 hours and then every 24 hours until negative; time to 50%, 90%, and 100% reduction in parasite density (PC(50), PC(90), and PCT); parasite reduction ratio at 24 and 48 hours (PRR(24) and PRR(48)); percentage of patients with undetectable parasitemia at 48 hours (PPUP(48)); time required to eradication; in vitro susceptibility to mefloquine and quinine by World Health Organization Microtest Mark III.


RESULTS
Of the study patients, 54.8% were immigrants from malaria-endemic countries. All the infections were acquired in Africa. All the patients were treated successfully. According to the pharmacodynamic parameters measured, no significant differences were recorded among patients with or without prior exposure to malaria. Pharmacodynamic comparison was performed between quinine and beta-arthemeter. Significantly higher clearance times were recorded for beta-arthemeter vs quinine (PC(50), PC(90), and PCT: 16.8, 42.6, and 72 h for quinine vs 7.9, 12.2, and 48 h for beta-arthemeter; p values: .02, < .0001, and .008, respectively). The number of patients who obtained a PPUP(48) with beta-arthemeter was higher than with quinine (66.7 vs 9.1%, p < .003), and PRR(24) was significantly higher in beta-arthemeter-treated patients (617 vs 3.15, p = .0001). PRR(48) and time to eradication were not measurable in the beta-arthemeter group (negative P at 48 h in most cases). Two recrudescences occurred after 5 and 7 days of beta-arthemeter monotherapy. All strains were fully susceptible to quinine and mefloquine.


CONCLUSIONS
Pharmacodynamic properties of mefloquine and quinine are in the range reported in literature. The better PCT and pharmacodynamics of beta-arthemeter suggest that it could be used as a first-line agent, coadministered with mefloquine.
Caramello
Pietro
P
Department of Infectious Diseases, Divisione A, Amedeo di Savoia Hospital, Turin, Italy.
Canta
Francesca
F
Cavecchia
Ilaria
I
Sergi
Giuseppina
G
Lipani
Filippo
F
Calleri
Guido
G
Gobbi
Federico
F
Di Perri
Giovanni
G
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000494:pharmacology*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D016778:Malaria, Falciparum / Q000150:complications / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage; D008875:Middle Aged; D018512:Parasitemia / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D021261:Parasitic Sensitivity Tests; D011803:Quinine / Q000008:administration & dosage; D016896:Treatment Outcome
D000962:Antimalarials; D037621:Artemisinins; D011803:Quinine; D000077549:Artemether; D015767:Mefloquine