Publication: Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria
Accepted Date
2008-10-31
Issued Date
2008-10-31
Copyright Date
2008
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
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Mahidol University
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BioMed Central
Bibliographic Citation
Ruangweerayut R, Looareesuwan S, Hutchinson D, Chauemung A, Banmairuroi V, Na-Bangchang K. Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria. Malar J. 2008 Oct 31;7:225.
Suggested Citation
Ronnatrai Ruangweerayut, รณไตร เรืองวีรยุทธ, Sornchai Looareesuwan, ศรชัย หลูอารีย์สุวรรณ, Hutchinson, David, Anurak Chauemung, Vick Banmairuroi, Kesara Na-Bangchang Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria. Ruangweerayut R, Looareesuwan S, Hutchinson D, Chauemung A, Banmairuroi V, Na-Bangchang K. Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria. Malar J. 2008 Oct 31;7:225.. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/710
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Title
Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria
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Abstract
BACKGROUND: This study investigated the pharmacokinetics of fosmidomycin when
given in combination with clindamycin at two dosage regimens in patients with
acute uncomplicated falciparum malaria.
METHODS: A total of 70 patients with acute uncomplicated Plasmodium falciparum
malaria who fulfilled the enrolment criteria were recruited in the
pharmacokinetic study. Patients were treated with two different dosage regimens
of fosmidomycin in combination with clindamycin as follows:Group I: fosmidomycin
(900 mg) and clindamycin (300 mg) every 6 hours for 3 days (n = 25); and Group
II: fosmidomycin (1,800 mg) and clindamycin (600 mg) every 12 hours for 3 days (n
= 54).
RESULTS: Both regimens were well tolerated with no serious adverse events. The
28-day cure rates for Group I and Group II were 91.3 and 89.7%, respectively.
Steady-state plasma concentrations of fosmidomycin and clindamycin were attained
at about 24 hr after the first dose. The pharmacokinetics of both fosmidomycin
and clindamycin analysed by model-independent and model-dependent approaches were
generally in broad agreement. There were marked differences in the
pharmacokinetic profiles of fosmidomycin and clindamycin when given as two
different combination regimens. In general, most of the dose-dependent
pharmacokinetic parameters (model-independent C(max): 3.74 vs 2.41 microg/ml;
C(max-ss): 2.80 vs 2.08 microg/ml; C(max-min-ss): 2.03 vs 0.71 microg/ml; AUC:
23.31 vs 10.63 microg.hr/ml (median values) were significantly higher in patients
who received the high dose regimen (Group II). However, C(min-ss) was lower in
this group (0.80 vs 1.37 microg/ml), resulting in significantly higher
fluctuations in the plasma concentrations of both fosmidomycin and clindamycin
following multiple dosing (110.0 vs 41.9%). Other pharmacokinetic parameters,
notably total clearance (CL/F), apparent volume of distribution (V/F, V(z)/F) and
elimination half-life (t(1/2z), t(1/2e)) were also significantly different
between the two dosage regimens. In addition, the dose-dependent pharmacokinetics
of both fosmidomycin and clindamycin tended to be lower in patients with
recrudescence responses in both groups.
CONCLUSION: The findings may suggest that dosing frequency and duration have a
significant impact on outcome. The combination of fosmidomycin (900 mg) and
clindamycin (300-600 mg) administered every six hours for a minimum of five days
would constitute the lowest dose regimen with the shortest duration of treatment
and which could result in a cure rate greater than 95%.
