+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria



Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria



Malaria Journal 7: 225



This study investigated the pharmacokinetics of fosmidomycin when given in combination with clindamycin at two dosage regimens in patients with acute uncomplicated falciparum malaria. 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). 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. 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%.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 030200667

Download citation: RISBibTeXText

PMID: 18973702

DOI: 10.1186/1475-2875-7-225


Related references

Evaluation of fosmidomycin, in combination with clindamycin, in adult patients with acute uncomplicated Plasmodium falciparum malaria. Journal Of Tropical Medicine & Parasitology: 1, 34-40. Ef, 2008

Inadequate efficacy of a new formulation of fosmidomycin-clindamycin combination in Mozambican children less than three years old with uncomplicated Plasmodium falciparum malaria. Antimicrobial Agents and ChemoTherapy 56(6): 2923-2928, 2012

Pharmacokinetics of the four combination regimens of dihydroartemisinin/mefloquine in acute uncomplicated falciparum malaria. Southeast Asian Journal of Tropical Medicine and Public Health 36(1): 23-33, 2005

Pharmacokinetics and pharmacodynamics of fosmidomycin monotherapy and combination therapy with clindamycin in the treatment of multidrug resistant falciparum malaria. Malaria Journal 6: 70, 2007

Short-course regimens of artesunate-fosmidomycin in treatment of uncomplicated Plasmodium falciparum malaria. Antimicrobial Agents and ChemoTherapy 49(9): 3749-3754, 2005

Pharmacokinetics of mefloquine with dihydroartemisinin as 2-day regimens in patients with uncomplicated falciparum malaria. Southeast Asian Journal of Tropical Medicine and Public Health 38(2): 205-212, 2007

Pharmacokinetics and bioequivalence evaluation of three commercial tablet formulations of mefloquine when given in combination with dihydroartemisinin in patients with acute uncomplicated falciparum malaria. European Journal of Clinical Pharmacology 55(10): 743-748, 2000

Comparative study of the effectiveness and pharmacokinetics of two rectal artesunate/oral mefloquine combination regimens for the treatment of uncomplicated childhood falciparum malaria. Annals of Tropical Paediatrics 27(1): 17-24, 2007

Evaluation of fosmidomycin in adults with acute uncomplicated Plasmodium falciparum malaria. Journal Of Tropical Medicine & Parasitology: 1, 28-33, 2008

Dynamics of Plasmodium falciparum parasitemia regarding combined treatment regimens for acute uncomplicated malaria, Antioquia, Colombia. American Journal of Tropical Medicine and Hygiene 83(1): 90-96, 2010

Fosmidomycin plus clindamycin for treatment of pediatric patients aged 1 to 14 years with Plasmodium falciparum malaria. Antimicrobial Agents and ChemoTherapy 50(8): 2713-2718, 2006

Pharmacokinetics of mefloquine, when given alone and in combination with artemether, in patients with uncomplicated falciparum malaria. Fundamental & Clinical Pharmacology 9(6): 576-582, 1995 ( ), 1996

Pharmacokinetics of mefloquine, when given alone and in combination with artemether, in patients with uncomplicated falciparum malaria. Fundamental and Clinical Pharmacology 9(6): 576-582, 1995

Population pharmacokinetics of mefloquine, administered as a fixed-dose combination of artesunate-mefloquine in Indian patients for the treatment of acute uncomplicated Plasmodium falciparum malaria. Malaria Journal 13: 187, 2014

Efficacy and Safety of Fosmidomycin-Piperaquine as Nonartemisinin-Based Combination Therapy for Uncomplicated Falciparum Malaria: A Single-Arm, Age De-escalation Proof-of-Concept Study in Gabon. Clinical Infectious Diseases 66(12): 1823-1830, 2018