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

• Published in: Malaria Journal
• Main Authors: Chauemung Anurak, Hutchinson David, Looareesuwan Sornchai, Ruangweerayut Ronnatrai, Banmairuroi Vick, Na-Bangchang Kesara
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2008
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-7-225; https://doaj.org/article/a13869ebb6384f74aafc1480a59561ce

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 μg/ml; C max-ss : 2.80 vs 2.08 μg/ml; C max-min-ss : 2.03 vs 0.71 μg/ml; AUC: 23.31 vs 10.63 μg.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 μg/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 ...