The fate of praziquantel in the organism I. Pharmacokinetics in animals

Abstract

The pharmacokinetics of 14C-praziquantel were tested in various species. Intravenously injected praziquantel is rapidly absorbed by the tissues in all species. The sum of unchanged drug and metabolites is rapidly eliminated from the intravascular space at a half-life of 3 hours (phase I) and 8 hours (phase II). The elimination for praziquantel itself, however, is considerably shorter, i. e. about 1 hour.After oral administration praziquantel was almost completely absorbed from the gastro-intestinal tract. Maximum serum concentrations were already reached within 30 min. to 1 hour. In rats absorption of the drug already from the stomach was observed.Non-metabolised praziquantel shows-due to an intense first pass effect in the liver-only very low maximum serum concentrations.All the species examined excrete the drug and its metabolites rapidly: within only 24 hours after administration the main portion of the administered HC-radioactivity was recovered in the excretion products. The kidneys are the predominant elimination path for praziquantel,The percentage of radioactivity eliminated with the bile in rats was 37 %of the dose within 7 hours after i. v, injection and 15 % of the dose after oral administration.Determination of the protein binding showed that 4(5 of the praziquantel is reversibly bound to serum proteins.

Serum concentrations and renal excretion in humans after oral administration of praziquantel — results of three determination methods —

“…This can be explained by the assump- The preponderance of metabolites, already evident during the absorption phase, indicates that the main quantity of enterally absorbed Praziquantel is metabolized during its first passage through the liver prior to its entry into the septemic circulation. A similar "first pass effect" was observed in corresponding animal experiements (2).…”

“…Extensive studies on the tolerance (1) and the pharmacokinetics using a 14C-Iabelled drug (2,3,4) were performed on laboratory animals.…”

In Vitro Metabolic Profile and in Vivo Antischistosomal Activity Studies of (η6-Praziquantel)Cr(CO)3 Derivatives

“…[17][18][19][20][21][22] As shown in Figure S3 in SI, PZQ was exclusively metabolized to its monohydroxylated species 1.M2 (cis-4-PZQ-OH) and 1.M5 (an unidentified mono-hydroxylated derivative). This observation is in good agreement with reports described earlier.…”

Cimetidine synergizes with Praziquantel to enhance the immune response of HBV DNA vaccine via activating cytotoxic CD8+T cell

“…[25][26][27] These observations prompted us to investigate whether CIM could act synergistically with PZQ to further enhance the immune responses on HBV DNA vaccine.…”