High-dose praziquantel for neurocysticercosis: serum and CSF concentrations

Abstract

Serum and CSF concentrations of praziquantel were analyzed in 8 patients with active neurocysticercosis aged 35 ± 16 (mean ± sd) years, in order to determine factors that may improve the therapeutic ratio. Praziquantel was given orally at 6‐h intervals for 10 days at a daily dose of 100 mg/kg. Serum concentrations were determined at 1, 2 and 4 h, and CSF concentrations at 2 h after the morning dose. Peak serum concentrations occurred between and 2 h after administration. There was a trend towards a drop in serum concentration from Days 1 through 5 to 10 of therapy. A fourfold increase in oral dose led to an eightfold rise in serum and CSF concentration, indicating saturation of hepatic metabolism. There were linear correlations (p < 0.01) between serum and CSF concentrations of praziquantel, indicating free flow across the blood‐brain barrier, above an apparent threshold, which may be related to occupation of plasma protein‐binding sites. The results indicate that monitoring of serum concentrations may be clinically useful.

Intestinal Lymphatic Delivery of Praziquantel by Solid Lipid Nanoparticles: Formulation Design,In VitroandIn VivoStudies

“…For its efficacy, safety, and comparative cost effectiveness, PZQ is included in the World Health Organization model list of essential drugs [4]. PZQ exhibits poor oral bioavailability because of its low aqueous solubility, extensive hepatic first-pass metabolism, and the short plasma half-life (0.8-1.5 hours) [5][6][7]. Although PZQ is a very effective anthelmintic, the above-mentioned shortcomings necessitate frequent administration of high oral doses of PZQ to overcome first-pass metabolism and to achieve sufficient plasma concentrations of PZQ at the larval tissues for eradication of cestode infection [8].…”