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The pharmacokinetics of oral doxycycline administered at 200 mg every 24 h were investigated in 17 patients recovering from severe Plasmodium falciparum malaria. The data suggest that the doses of doxycycline currently recommended (circa 3.5 mg/kg of body weight daily) may not be optimal

In the study reported here, the diagnostic performance of two new rapid tests for the diagnosis of malaria was evaluated in symptomatic patients in a non-endemic area. Of 557 consecutive patients, 109 (19.6%) had documented malaria. For the NOW ICT MALARIA P.f./P.v. (Binax, Portland, ME, USA) and OptiMAL IT (Diamed, Cressier, Switzerland) tests, respectively, sensitivity values were 96.3% and 79.8% (P-value, 0.0001), and specificity values were 98.8% and 98.4%. The NOW ICT test did not detect two of 80 Plasmodium falciparum infections, and it generated false-positive results for five patients. The OptiMAL IT test failed to detect ten of the P. falciparum infections, and it generated seven false-positive results. The results suggest that these rapid diagnostic tests for malaria may be useful, but they cannot replace microscopic examination of blood films.

The population pharmacokinetics of pyrimethamine (PYR) and sulfadoxine (SDX) for a group of 32 children with congenital toxoplasmosis was investigated by nonparametric modeling analysis. A one-compartment model was used as the structural model, and individual pharmacokinetic parameters were estimated by Bayesian modeling. PYR (1.25 mg/kg of body weight) and SDX (25 mg/kg) were administered orally every 10 days for 1 year, with adjustment of the dose to body weight every 3 months. Drug concentrations were measured by high-performance liquid chromatography. A total of 101 measurements in serum were available for both drugs. Mean absorption rate constants, volumes of distribution, elimination rate constants, and half-lives were 0.915 h ؊1 , 4.379 liters/kg, 0.00839 h ؊1 , and 5.5 days for PYR and 1.659 h ؊1 , 0.392 liters/kg, 0.00526 h ؊1 , and 6.6 days for SDX, respectively. Wide interindividual variability was observed. The estimated minimum and maximum concentrations of PYR in serum differed 8-and 25-fold among patients, respectively, and those of SDX differed 4-and 5-fold, respectively. Increases in the concentration of PYR were observed for eight children, and increases in the SDX concentration were observed for seven children. Serum PYR-SDX concentrations are unpredictable even when the dose is standardized for body weight. The concentrations of the PYR-SDX combination that are most efficacious for children have not yet been established. A model such as ours, associated with long-term follow-up, is needed to study the correlation between exposure to these two drugs and clinical outcome in children.Toxoplasma gondii is a ubiquitous intracellular protozoan parasite. Infection during pregnancy can result in fetal infection, leading to severe congenital defects such as hydrocephalus, mental retardation, and retinochoroiditis that may be present at birth or may develop later in life (36). Although no well-controlled clinical trials have been carried out to assess its efficacy and safety in children, early treatment is believed to prevent late-onset sequelae. A bibliographical analysis revealed up to 20 different therapeutic antiparasitic regimens (27). Most of them included courses of a combination of pyrimethamine (PYR) and a sulfonamide (sulfadiazine or sulfadoxine [SDX]). However, pharmacokinetic (PK) data for these drugs are scarce, especially for pediatric populations (6,17,23,48), mainly because of the reluctance to pursue PK studies on children. Consequently, many therapeutic agents, such as PYR and SDX, have not been studied adequately in children (24). However, for the past 2 decades, this problem has been addressed by use of the population-based PK approach and the Bayesian method. PK parameter values and their interindividual variability can be determined even when only sparse blood samples are available from a homogeneous or heterogeneous population. Such methodologies can be used even if only one concentration measurement per patient is available (41).Very few studies of the pharmacokinetics of PYR an...

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