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F Verdier

Publications and source records attributed to F Verdier.

83 records · Page 5Linked to original sources
PubMedDate not supplied

Intrarectal Quinimax (an association of Cinchona alkaloids) for the treatment of Plasmodium falciparum malaria in children in Niger: efficacy and pharmacokinetics.

In an attempt to avoid the complications associated with intramuscular quinine administration, we assessed the intrarectal route. Sixty-six children aged from 2 to 10 years with Plasmodium falciparum malaria were included in the study, which took place in Niamey, Niger. Fifty-five children were given 20 mg/kg of the diluted injectable form of Quinimax (a quinine, quinidine, cinchonine, cinchonidine association) intrarectally. A further 11 children with malaria were treated with 12.5 mg/kg of the same Quinimax solution by the intramuscular route. All the children were treated twice a day for 3 d. Blood samples were drawn from 20 children (15 treated intrarectally and 5 intramuscularly) for a kinetic study. Both modes of administration were well tolerated. Mean fever clearance times (+/- standard errors) were 48.6 +/- 2.7 h and 35.9 +/- 2.2 h in the intrarectal and intramuscular groups, respectively (P = 0.05). Mean parasite clearance times (+/- standard errors) and mean times to achieve 50% reduction in parasitaemia (+/- standard errors) were similar after intrarectal (46.5 +/- 5.7 h and 7.8 +/- 0.9 h respectively) and intramuscular administration (27.4 +/- 3.6 h and 8.7 +/- 1.7 h, respectively). Tmax. after intrarectal administration (2.7 +/- 0.4 h) did not differ significantly from the value after intramuscular administration (1.1 +/- 0.6 h), but Cmax. and the area under the concentration-time curve from 0 to 48 h were lower (4.9 +/- 0.6 mg/L and 230.0 +/- 9.6 mg/L.h, respectively) than after intramuscular administration (9.1 +/- 1.2 mg/L and 356.0 +/- 4.2 mg/L.h, respectively) (P < 0.001). Compared to the intramuscular route, intrarectal Quinimax bioavailability was 40%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Rectal↗
PubMedDate not supplied

An open randomized clinical study of intrarectal versus infused Quinimax for the treatment of childhood cerebral malaria in Niger.

The intrarectal route has been shown to be an alternative to parenteral therapy for the treatment of acute uncomplicated malaria. We conducted an open randomized clinical study of intrarectal Quinimax (a Cinchona alkaloids association) (20 mg/kg, then 15 mg/kg every 8 h) vs. intravenous Quinimax (8 mg/ kg infused over 4 h every 8 h) for 2 d in 76 children (39 in the intrarectal and 37 in the infusion groups) with cerebral falciparum malaria in Niger. This treatment was followed by oral chloroquine (10 mg/kg/d for 3 d). The primary end points of the study were fatal outcome and coma recovery time. In the intrarectal group, 35 children were cured (90%) and 4 died. In the infused group, 28 were cured (76%) and 9 died; mean coma recovery times were 34.6 h (SD = 12.8) and 33.0 h (SD = 14.1) for the intrarectal and infused groups, respectively. None of the differences was significant. Both treatments were well tolerated and no anal irritation was observed with intrarectal Quinimax. These findings suggest that intrarectal Quinimax can be an alternative to intravenous administration for rapid onset childhood cerebral malaria in the rural tropics, where the safety of parenteral administration cannot be guaranteed.

Administration, Rectal↗
PubMedDate not supplied

[Intrarectal administration of quinine: an early treatment for severe malaria in children?].

Delay for treatment of severe malaria is the cause of an important childhood mortality in Africa especially in rural zone when health facilities and accessibility are scarce. Intrarectal treatment is of particular interest in children as a non aggressive, painless and easy treatment. It can be used as early treatment and could decrease the lethality of severe malaria. We recently showed the kinetic profile, the optimal regimen and the clinical efficacy of intrarectal quinine (QIR) using Quinimax (Sanofi, Gentilly France) 20 mg/kg in solution with 2 ml of water. From 1994 to 1996 two open clinical trials were performed in Niger in children (2-15 years). QIR was compared with intraveinous infusion in cerebral malaria (n = 76) and with intramuscular quinine in severe malaria (n = 57). A three daily QIR administration (20 mg/kg followed by 15 mg/kg/8 h) was used in cerebral malaria; a two daily administration in severe malaria (30 mg/kg followed by 20 mg/kg/12 h). Symptomatic treatment was associated for hyperthermia, hypoglycemia, anemia and seizures. Results. In the cerebral malaria study 58 children presented a Blantyre coma score below 3. Four children in the IR group and 9 children in the infusion group died (P > 0.05). Evolution was similar in both treatment groups: temperature clearance (< 37.5 degrees C) 39.0 +/- 15.2 h and 37.1 +/- 16.5 h; return to consciousness 34.6 +/- 12.8 h and 33.0 +/- 14.1 h; decrease to 50% of the initial parasites count: 15.5 +/- 11.5 h and 13.8 +/- 10.0 h. Residual blood quinine concentrations at 48 hours were similar 7.4 +/- 3.7 mg/l and 7.2 +/- 2.9 mg/l. In the severe malaria study, the mortality was 0 and 7.6% in the QIR and IM group respectively (P > 0.005). Evolution was similar in both treatment groups: temperature clearance (< 37.5 degrees C) 38.7 +/- 22.8 h and 38.6 +/- 22.2 h; return to consciousness 26.8 +/- 13.9 h and 27.6 +/- 9.9 h for the 16 children in coma. The evolution under QIR treatment was also similar with that described with the other quinine routes. QIR allows an efficious treatment particularly when correct infusion cannot be performed. The efficacy, the simplicity and the good tolerance of QIR are of major concern to decrease the mortality of severe malaria due to delay for treatment and to decrease the side-effects due to intramuscular administrations of quinine in Africa.

Administration, Rectal↗
PubMedDate not supplied

[Phenytoin and the popliteal lymph node test in the Sprague-Dawley rat].

The detection of xenobiotics which the potential to induce autoimmune reactions is currently hardly possible. The popliteal lymph node assay initially developed in mice may prove useful in this regard. Results obtained with phenytoin in Sprague Dawley rats are presented. Single doses of phenytoin were injected into one hind footpad and the popliteal lymph node was excised and weighed 3, 7 or 10 days after injection. Only the 5 mg dose level produced a significant increase in popliteal lymph node weight, structural and cellular changes in the lymph node indicating a humoral stimulation was noticed in the males at 2 mg and in the males and females at 5 mg. These results warrant further progress in the development of this assay.

Animals↗
PubMedDate not supplied

[Pharmacokinetics of antimalarials: quinine and mefloquine, halofantrine, qinghaosu, amino-4-quinolines].

The development of new sensitive and specific assays (HPLC) have enabled the pharmacokinetics of antimalarial drugs to be studied. Parameters such as half-life distribution volume, clearance and bioavailability, are defined. In healthy subjects, quinine is rapidly eliminated (t1/2 beta: 6-12 h). Hepatic biotransformation accounts for approximately 80% of its total clearance. In malaria, the pharmacokinetic properties of quinine (decrease in the apparent volume of distribution, prolongation of the t1/2 beta, reduction in systemic clearance), are altered in proportion to the severity of infection. Red cell concentrations and plasma binding are increased. Parenteral quinine should be given by slow intravenous infusion and a loading dose is recommended in severe infections. Chloroquine (t1/2 beta: 6-50 days) and mefloquine (t1/2 beta: 6-33 days) have extensive tissue distribution and prolonged activity after a single dose. Both drugs are concentrated in erythrocytes and are bound considerably to plasma proteins. Amodiaquine is not found in the blood after oral administration. Hepatic biotransformation accounts for almost all orally administered drug. Its antiplasmodial activity is thus almost entirely due to monodesethylamodiaquine, the main metabolite. In healthy subjects, the t1/2 beta of this metabolite is 9 to 18 days in plasma. Amodiaquine is concentrated in erythrocytes. The protein binding of this drug has not been studied to date. For prophylaxis, it has been suggested that the dosage of 10 mg/kg/wk should be spread over the week (3.5 mg/kg every other day, or 1.5 every day). Halofantrine has an elimination half-life of between 1.3 and 6.6 days. This drug has been suggested as a single-dose treatment. No pharmacokinetic studies of qinghaosu have been reported in humans. In rabbits, the elimination half-life in plasma was found to be 40 min. Although rapidly eliminated, this drug appears to be highly effective. More information is required on the pharmacokinetics of these drugs in malaria, during pregnancy, in children and in renal and hepatic failure.

Adult↗