title: Effects of encapsulation of primidone on its oxidative metabolism in rats.
abstract: The aim of this study was to evaluate the influence of primidone (PRM) nanoencapsulation on its metabolism. Suspensions of PRM powder and PRM-loaded poly-epsilon-caprolactone nanocapsules were administered orally in the same way to rats. Primidone-loaded poly-epsilon-caprolactone nanocapsules were prepared according to the interfacial deposition technique. Free PRM suspensions were obtained by addition of PRM powder to a suspension of 0.212% carboxymethylcellulose CMC 12H in water. The dose was 20 mg/kg, n = 6, for each experiment. Urinary and faecal levels of PRM and of its three major metabolites, phenylethylmalonamide (PEMA), phenobarbital (PB), and p-hydroxyphenobarbital (p-HO-PB), were determined. Concentrations were evaluated by high-performance liquid chromatography (HPLC) according to a validated analytical method. After PRM nanocapsule administration, non-metabolised PRM urinary levels were increased compared to those observed after administration of a suspension of primidone powder (43.7+/-8.8% after PRM-loaded nanocapsule and 37.7+/-8.1% after free PRM administration). For phenylethylmalonamide, no difference was observed in urinary excretion in the two cases. For two of the oxidised metabolites, PB and p-HO-PB, excretion was delayed and shortened. The amount of these oxidised metabolites was lowered from 0.95% after free PRM administration to 0.25% after PRM-loaded nanocapsule administration. No difference was noted in non-metabolised primidone excretion in faeces. These results suggest that primidone-loaded nanocapsules could be used as a vehicle for oral primidone administration in order to minimise the phenobarbital metabolic pathway.
authors.affiliation: Laboratoire de Pharmacochimie, Faculté de Médecine et de Pharmacie de Rouen, France.
authors.forename: V
authors.initials: V
authors.lastname: Ferranti
authors.forename: C
authors.initials: C
authors.lastname: Chabenat
authors.forename: H
authors.initials: H
authors.lastname: Marchais
authors.forename: S
authors.initials: S
authors.lastname: Ménager
authors.forename: H
authors.initials: H
authors.lastname: Hue
authors.forename: A M
authors.initials: AM
authors.lastname: Orecchioni
authors.forename: O
authors.initials: O
authors.lastname: Lafont
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004339:Drug Compounding; D005243:Feces / Q000737:chemistry; D005260:Female; D036103:Nanotechnology / Q000379:methods; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D010657:Phenylethylmalonamide / Q000378:metabolism / Q000652:urine; D011091:Polyesters; D011324:Primidone / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000927:Anticonvulsants; D011091:Polyesters; D011324:Primidone; C016240:polycaprolactone; C017414:4-hydroxyphenobarbital; D010657:Phenylethylmalonamide; D010634:Phenobarbital