Pharmacokinetic Pattern of Menbutone in Calves after Single Intravenous and Intramuscular Administration
Raquel Diez | Jose M. Rodriguez | Cristina Lopez | Raul de la Puente | Matilde Sierra | M. Jose Diez | Nelida Fernandez | Juan J. Garcia | Ana M. Sahagun
Menbutone is a choleretic agent currently used in Europe to treat digestive disorders in livestock and dogs. Pharmacokinetic parameters were established in 4-month Holstein calves after intravenous (IV) and intramuscular (IM) administration. The drug was administered to 12 animals (10 mg/kg) for both IV and IM routes following a crossover design. Plasma samples were collected at various time points over 24 h and analyzed by reverse-phase high-performance liquid chromatography with a photodiode-array detector, following a method validated according to European Medicines Agency guidelines. Pharmacokinetic parameters were calculated using compartmental and non-compartmental methods. Menbutone followed a two-compartment open model after IV injection, with a total clearance (Cl) of 71.9 ± 13.5 mL/h/kg, an elimination half-life (t<sub>½β</sub>) of 4.53 ± 2.45 h, and a volume of distribution at steady-state (V<sub>ss</sub>) of 310.4 ± 106.4 mL/kg. Non-compartmental elimination half-life (t<sub>½λ</sub>) was 4.2 ± 1.1 h. After IM administration, drug pharmacokinetics was best described by a one-compartment open model. The peak plasma concentration (C<sub>max</sub>) was 15.1 ± 4.3 µg/mL; the time to reach C<sub>max</sub> (t<sub>max</sub>), 1.66 ± 0.55 h; and the mean absorption time (MAT), 2.50 ± 1.42 h. Absorption was high, with a fraction of the dose absorbed (F) of 83.5 ± 22.4%. Menbutone was rapidly eliminated from plasma for both routes of administration, with a fast and high IM bioavailability.
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