Indications
Praziquantel is indicated for patients aged one year and older for the treatment of schistosomiasis caused by all species of Schistosoma, including Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni, and Schistosoma hematobium. Additionally, it is prescribed for clonorchiasis and opisthorchiasis resulting from liver flukes such as Clonorchis sinensis and Opisthorchis viverrini. The endorsement for this indication arises from clinical studies wherein these two fluke species were not distinctly differentiated.
Pharmacodynamics
Praziquantel acts on trematodes and cestodes by inducing rapid muscular contractions through a targeted effect on cell membrane permeability, leading to vacuolization and disintegration of the schistosome tegument. Its efficacy is pronounced against adult worms in comparison to younger stages. The drug promotes increased calcium ion influx, which is thought to play a crucial role in this process. Secondary effects include inhibited glucose uptake, decreased glycogen levels, and stimulated lactate release. The action of Praziquantel is specific to trematodes and cestodes, leaving nematodes, including filariae, unaffected. However, it exhibits limited efficacy against migrating schistosomulae, and its effectiveness against juvenile schistosomes diminishes until three to four weeks post-infection, before increasing to full efficacy by six to seven weeks.
Absorption
After oral administration, approximately 80% of the Praziquantel dose is absorbed. In individuals with normal hepatic function who received a dose of 40 mg/kg under fasting conditions, the mean ± SD maximum plasma concentration (Cmax) and area under the curve (AUC) were observed to be 0.83 ± 0.52 µg/mL and 3.02 ± 0.59 µg/mL x hr, respectively, with a time to peak concentration (Tmax) of 1.48 ± 0.74 hours.
Metabolism
Praziquantel is swiftly metabolized via the cytochrome P450 enzyme system and undergoes a significant first-pass effect following oral administration, which influences its bioavailability and systemic circulation levels.
Mechanism of Action
Praziquantel is believed to exert its effects by targeting the β subunits of voltage-gated calcium channels, specifically in the parasites Schistosoma mansoni and Schistosoma japonicum. This hypothesis stems from the absence of two conserved serine residues in these subunits, which may play a role in the drug's selective action. Supporting this theory, the resistance of approximately 50% of Schistosoma mansoni to praziquantel is observed when calcium channel blockers such as nicardipine and nifedipine are co-administered. Additionally, praziquantel treatment has been associated with an increased exposure of antigens on the parasite's surface, although further research is required to fully elucidate this mechanism of action.
