In vitro characterization of some biopharmaceutical properties of praziquantel.
In several studies of patients with neurocysticercosis under treatment with praziquantel (PZQ), the pharmacokinetic data were difficult to interpret probably because of the low solubility as well as its variable oral bioavailability. Because there is limited information available regarding the biopharmaceutical properties of PZQ, the aim of this work was to evaluate the absorption characteristics of the drug and its dissolution behaviour in simulated media. Additionally, its in vitro protein binding and displacement by highly bound drugs was evaluated. Permeability evaluation was carried out by using Caco-2 cells. Dissolution release profiles were evaluated using the USP apparatus and the following dissolution media: HCl containing 2mg of sodium laurylsulfate per milliliter, milk, FeSSIF and FaSSIF. Protein binding of PZQ was carried out by equilibrium dialysis. Results showed that praziquantel was absorbed by passive diffusion. The apparent permeability constant value was 4.4x10(-5) cm/s. Binding was not influenced by the addition of highly bound drugs. Dissolution from a tablet formulation showed that the rate of praziquantel was dependent on the components of the media. Although the simulated media could explain the influence of the lipids on praziquantel absorption, they were not able to forecast the influence of carbohydrates. Further refinements are required to explain the in vivo data.
González-Esquivel
Dinora
D
Laboratorio de Neuropsicofarmacología, Instituto Nacional de Neurología y Neurocirugía, Insurgentes sur 3877, La Fama, Tlalpan 14269, México D.F., México.
Rivera
Julio
J
Castro
Nelly
N
Yepez-Mulia
Lilian
L
Jung Cook
Helgi
H
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D018938:Caco-2 Cells; D002417:Cattle; D006801:Humans; D008892:Milk; D011223:Praziquantel / Q000737:chemistry* / Q000493:pharmacokinetics; D011485:Protein Binding; D012995:Solubility
D001798:Blood Proteins; D011223:Praziquantel