Pharmacokinetics of intravenously, intramuscularly and intra‐adiposely administered carazolol in pigs

Abstract

The beta-blocking agent carazolol is used for the prevention of stress syndromes in pigs. Little is known of the pharmacokinetics of this drug, and therefore of its residue status in meat. In this study carazolol pharmacokinetics were investigated in a randomized three-way cross-over design in five pigs. A dose of 0.025 mg/kg was given intravenously, intramuscularly and intra-adiposely (in the subcutaneous fat layer). Carazolol was rapidly distributed and had a short half-life of 1.2-4.2 h. The distribution volume was calculated to be 0.22-0.65 l/kg. After intramuscular or intra-adipose administration the absorption pattern was biphasic. A rapid initial phase was followed by a slow second phase. Absorption was found to be incomplete at 24 h after intramuscular and intra-adipose administration ranging from 24 to 59% and 25 to 66%, respectively. The biphasic behaviour could be explained by retention of the drug in the tissues after absorption of the solvent was complete. A few hours after intravenous administration only negligible amounts of the drug were circulating in the body; however, considerable amounts of drug might have remained at the intramuscular or intra-adipose injection site.

Investigation of Drug Delivery in Rats via Subcutaneous Injection: Case Study of Pharmacokinetic Modeling of Suspension Formulations

“…Other routes of administration have been explored to enable the evaluation of early efficacy and safety of compounds without investing a significant amount of effort in the optimization of the compounds' properties. Subcutaneous (SC) administration is a popular alternative delivery route as it provides a number of advantages, [1][2][3][4][5][6] such as (1) potential to circumvent first pass metabolism and promote the effective delivery of drugs that have low oral bioavailability, thus achieving the desired exposure in animals without frequent dosing (i.e., attaining C min with a single SC injection), (2) potential to achieve improved tolerability by minimizing the peak to trough ratio in the systemic circulation, (3) potential to achieve prolonged systemic exposure through administration of a simple suspension formulation without concerns of vehicle-related effects that may convolute in vivo results, and (4) expanded library of dosing vehicles when compared to IV administration.…”

“…According to the literatures, absorption via the SC route can be influenced by a compound's physiochemical properties such as charge, molecular weight, hydrophilicity, drug concentration (solubility), injection volume, ionic strength, and pH. [1][2][3][4][5][6][7][8][9][10][11][12][13] Furthermore, the control of absorption process between small molecules and protein therapeutics will be different and can be further influenced by formulation. This article, we focused our study on the small molecules.…”

Effects of an allostatic modulator on the behavior and blood indicators of young bulls after transport

“…8 Several AM substances have been developed, such as dopaminergic antagonists 9 and β-adrenergic receptor blockers. 10 In addition, vitamins, [11][12][13] microelements, 14,15 and amino acids 13 have also been tested. Improvements have been observed recently in blood indicators and meat color parameters in 18-to 20-month-old bulls fed with 10 g/head/d of an AM composed of acetylsalicylic acid, ascorbic acid, sodium chloride and potassium chloride for 30 d preslaughter.…”