Pharmacokinetics of Propranolol and Its Metabolites in Horses after Intravenous or Oral Administration.

Abstract

The pharmacokinetics characteristics of propranolol (PPL) in horses was studied by administering the drug intravenously or orally to the animals. The predominant primary pathway was ring oxidation, and 4-hydroxypropranolol glucuronide (4-OHPG) was the major metabolite in both plasma and urine. Side-chain glucuronidation and oxidation were not significant. A two-compartment model was employed for PPL followed by a one-compartment model for 4-OHPG. After oral administration, one-step absorption and two-step first pass metabolism were employed. The fraction absorbed of PPL was approximately 70% after oral administration, and the bioavailability varied among individual horses from 1 to 79% depending on the first pass metabolism. The biologic half-life (T1/2) of PPL obeys the allometric equation in some animal species including rats and horses, except for human. T 1/2 of PPL in horses was approximately 2 h.

Densitometry and indirect normal‐phase HPTLC–ESI–MS for separation and quantitation of drugs and their glucuronide metabolites from plasma

“…The same approach was applied to estimate ASE and ASE‐G from human urine with a linear working range of 0.500–100 and 10.0–3000 ng/mL, respectively (de Boer et al, ). Methods to analyze PRO and PRO‐G are largely intended to study their disposition in rat plasma (Beaudry et al, ), horse plasma (Aramaki et al, ), human plasma (Luan et al, ) and various organs of mice such as brain, lung, kidney and liver (Salomonsson et al, ), with little information on quantitative analysis. TEL‐G has been determined in the concentration range 0.5–100 ng/mL from rat plasma after protein precipitation with acetonitrile using LC–MS/MS technique (Li et al, ).…”

“…In the present work an attempt is made to separate and quantify three selected drugs, namely asenapine (ASE), propranolol (PRO) and telmisartan (TEL) and their phase II glucuronide metabolites (Figure ) using TLC–densitometry and indirect sampling HPTLC–MS. The literature presents few methods to study these drug–metabolite pairs using LC–MS/MS (Aramaki, Mori, Nakata, Shinohara, & Koizumi, ; Beaudry et al, ; de Boer et al, ; de Boer et al, ; Kertesz & Van Berkel, ; Li et al, ; Luan, Shao, Ma, & Zeng, ; Patel et al, ; Salomonsson, Bondesson, & Hedeland, ). ASE and asenapine‐ β ‐ d ‐glucuronide (ASE‐G) along with other metabolites have been determined in human plasma (de Boer et al, ) and urine (de Boer et al, ).…”

Pharmacokinetics and pharmacodynamics of oral and intravenous metoprolol tartrate in clinically healthy horses

“…Currently, equine PK and limited PD data are available for 2 ß‐blockers: intravenous propranolol, a non‐selective, first generation ß‐blocker, and oral sotalol, a class III antiarrhythmic with weak ß‐blocker properties (Aramaki et al, 2000; Broux et al, 2016; Broux et al, 2018). To date, PK data for an orally administered, cardioselective ß‐blocker have not been described for the horse.…”