Pharmacokinetics of ricobendazole in calves

Abstract

The pharmacokinetics of ricobendazole (RBZ) and its major metabolite albendazole sulphone (ABZSO2) were studied in six calves, after administration of RBZ (7.5 mg/kg), using a 10% experimental solution by the intravenous (i.v.) route, a 10% commercial solution by the subcutaneous (s.c.) route, and a 10% experimental suspension by the intraruminal (i.r.) route. Blood samples were drawn during a 60-h period. Plasma drug and metabolite concentrations were determined by HPLC. The pharmacokinetic evaluation in each case was prepared by weighted least-squares nonlinear regression analysis. Ricobendazole i.v. data were best fitted by a two-compartment model. The best pharmacokinetic exponents and coefficients were estimated, and the pharmacokinetic variables for RBZ and ABZSO2 were calculated from them. Similar patterns of plasma disposition were found for RBZ after i.r. and s.c. administration, suggesting delayed release from the s.c. site resembling the slow release of the drug from the rumen.

Physicochemical Characterization of Ricobendazole: I. Solubility, Lipophilicity, and Ionization Characteristics

“…[3][4][5][6] The injection is formulated as a highly acidic solution with additional solubilization by organic co-solvents. 5 Reports have indicated that it is effective as an anthelmintic agent 8,[20][21][22] but causes injection site reactions, 5 so alternative better tolerated formulations are sought. The dosage administered in efficacy and pharmacokinetic studies varied from 3.75 6 to 7.5 mg/kg.…”

“…The mixtures were then centrifuged at 3000 rpm for 10 min and the aqueous layer taken for analysis by HPLC. Experiments were repeated five times and apparent partition coefficients (P) were calculated using Equation 5.…”

“…Pharmacokinetic studies following intravenous and subcutaneous administration of 150 mg/mL RBZ solution (Bayverm PI 1 , Bayer, Argentina) have shown rapid absorption occurs following subcutaneous administration but only low bioavailability (36.8%). 4 Formentini et al 5 also describe the pharmacokinetics following subcutaneous administration of another RBZ solution formulation containing 10% RBZ in a vehicle composed of propylene glycol, polyvinylpyrrolidone, hydrochloric acid, and water at pH 1.05 (Sintyotal-R 1 , Biogenesis, Argentina). Similar bioavailability was reported (F ¼ 40.5%) and swelling and drug precipitation at the injection site were noted.…”

“…Similar bioavailability was reported (F ¼ 40.5%) and swelling and drug precipitation at the injection site were noted. 5 Although the reported RBZ injections appear to overcome the slow and variable absorption seen with oral administration of ABZ, the low bioavailability and injection site reactions indicate the injectable form is not optimal. To enable development of novel formulations further information on RBZ physicochemical properties is required.…”

Simultaneous determination of albendazole and praziquantel in rat plasma by HPLC-UV

“…Albendazole [ABZ] is an inactive moiety but it readily gets metabolized to an active metabolite Albendazole sulfoxide [ABZSO] then this ABZSO is then further metabolized to an inactive metabolite Albendazole sulfone [ABZSO2] [10]. As ABZ is metabolized extensively, therefore, the plasma concentration of ABZ is also very low as a result the pharmacokinetic studies were been done using Albendazole sulfoxide [ABZSO] as an active metabolite and Albendazole sulfone [ABZSO2] as an inactive metabolite [11][12][13][14][15]. Metabolism of Praziquantel [PRQ] occurs giving a number of hydroxylated metabolites [16][17][18], among which the active metabolite is mainly trans-4-hydroxypraziquantel [TRANS], an active metabolite [19].…”