pharmaceutics Article Pharmacokinetics and Bioavailability of Carprofen in Rainbow Trout (Oncorhynchus mykiss) Broodstock Kamil Uney 1, *, Duygu Durna Corum 2 , Ertugrul Terzi 3 and Orhan Corum 2   Citation: Uney, K.; Durna Corum, D.; Terzi, E.; Corum, O. Pharmacokinetics and Bioavailability of Carprofen in Rainbow Trout (Oncorhynchus mykiss) Broodstock. Pharmaceutics 2021, 13, 990. https://doi.org/10.3390/ pharmaceutics13070990 Academic Editors: Patrícia Severino, Arnobio A. da Silva-Junior, Classius Ferreira Da Silva and Raquel De M.Barbosa Received: 4 June 2021 Accepted: 25 June 2021 Published: 30 June 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, Konya 42130, Turkey 2 Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Kastamonu, Kastamonu 37150, Turkey; ddurna@kastamonu.edu.tr (D.D.C.); orhancorum@kastamonu.edu.tr (O.C.) 3 Faculty of Fisheries, University of Kastamonu, Kastamonu 37150, Turkey; ertugrulterzi@gmail.com * Correspondence: kuney@selcuk.edu.tr; Tel.: +90-332-223-2733 Abstract: The aim of this study was to determine the pharmacokinetics of carprofen following intra- venous (IV), intramuscular (IM) and oral routes to rainbow trout (Oncorhynchus mykiss) broodstock at temperatures of 10 ± 1.5 ◦ C. In this study, thirty-six healthy rainbow trout broodstock (body weight, 1.45 ± 0.30 kg) were used. The plasma concentrations of carprofen were determined using high-performance liquid chromatography and pharmacokinetic parameters were calculated using non-compartmental analysis. Carprofen was measured up to 192 h for IV route and 240 h for IM, and oral routes in plasma. The elimination half-life (t 1/2λz ) was 30.66, 46.11, and 41.08 h for IV, IM and oral routes, respectively. Carprofen for the IV route showed the total clearance of 0.02 L/h/kg and volume of distribution at steady state of 0.60 L/kg. For IM and oral routes, the peak plasma concen- tration (C max ) was 3.96 and 2.52 μg/mL with the time to reach C max of 2 and 4 h, respectively. The bioavailability was 121.89% for IM route and 78.66% for oral route. The favorable pharmacokinetic properties such as the good bioavailability and long t 1/2λz for IM and oral route of carprofen suggest the possibility of its effective use for the treatment of various conditions in broodstock. Keywords: bioavailability; broodstock; carprofen; pharmacokinetics; rainbow trout 1. Introduction Analgesic drugs are indispensable for pain management in mammals; however, their use in fish remains limited [1]. In recent years, with the increasing awareness of animal welfare, the management of pain and inflammation in fish under human care has been emphasized [2]. Although it is believed that there is no pain perception in fish, studies have shown that they have nociceptors responsible for transmission of painful stimulation, similar to mammals [3]. In various fish species, adverse changes in behavior and physi- ology in response to negative noxious stimuli were attenuated by the administration of analgesics [3]. Analgesic drugs are recommended for surgical operations, trauma-related injuries, cutaneous ulceration, and inflammatory lesions in fish [4]. Opioids and non- steroidal anti-inflammatory drugs (NSAIDs) are frequently used for pain control in fish [1]. In clinical trials, opioid use has caused side effects on cardiovascular and respiratory sys- tems in fish; however, no adverse effects have been reported for NSAIDs [1]. NSAIDs have reduced postsurgical muscle damage in koi carp and minimal anesthetic concentration in goldfish and resulted in faster post-pain feeding in rainbow trout [3]. Pain and inflammation are associated with cyclooxygenase enzymes (COX-1 and COX-2), mostly COX-2, which is involved in the synthesis of prostaglandins (PGs) found at high levels at inflamed sites [5]. COX-1 is constitutively expressed in most tissues and synthesizes PGs that play a role in maintaining of normal physiological functions. COX-2 exists in an inducible form and its release increases during the inflammatory process in different cell types [6]. It has been demonstrated that the COX-2 enzyme, which has been Pharmaceutics 2021, 13, 990. https://doi.org/10.3390/pharmaceutics13070990 https://www.mdpi.com/journal/pharmaceutics