# Pharmacokinetic Pattern of Menbutone in Calves after Single Intravenous and Intramuscular Administration

## TL;DR

This study investigates how the drug menbutone is processed in calves after being given through different routes, revealing how quickly it is absorbed and eliminated.

## Contribution

The first pharmacokinetic study of menbutone in cattle, providing key parameters for intravenous and intramuscular administration.

## Key findings

- Menbutone has a moderate volume of distribution and fast elimination after intravenous administration.
- Intramuscular administration leads to rapid absorption with high bioavailability in calves.
- Pharmacokinetic parameters were calculated using validated methods and showed consistent elimination patterns.

## Abstract

Menbutone is a drug that increases hepato-digestive secretions and has been used for more than 50 years in Europe to treat a wide number of digestive disorders in livestock and dogs. However, despite this use, little is known about its pharmacokinetics, more specifically in cattle. This work contributes to a better knowledge of the pharmacokinetics of menbutone when administered intravenously and intramuscularly to cattle (12 Holstein calves), being the first study to describe it in this animal species. After intravenous administration, the drug showed a moderate volume of distribution and a fast elimination from the body. After intramuscular administration, menbutone exhibited quick and high absorption.

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 (t½β) of 4.53 ± 2.45 h, and a volume of distribution at steady-state (Vss) of 310.4 ± 106.4 mL/kg. Non-compartmental elimination half-life (t½λ) was 4.2 ± 1.1 h. After IM administration, drug pharmacokinetics was best described by a one-compartment open model. The peak plasma concentration (Cmax) was 15.1 ± 4.3 µg/mL; the time to reach Cmax (tmax), 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.