Prapansak Srisapoome
Lisa A. Tell
Chi-Chung Chou- 1Department of Aquaculture, Faculty of Fisheries, Kasetsart University, Bangkok, Thailand
- 2Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
- 3Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan
Editorial on the Research Topic
Aquatic Pharmacology, Volume II: Pharmacokinetics for Aquatic Species
The second edition of Aquatic Pharmacology features six articles, of which five belong to the discipline of pharmacokinetics and one on the anti-fungal activity of disinfectants. Further breakdown of the topics in this edition, include three pharmacokinetic manuscripts on fluoroquinolones (Shan et al.; Song et al.; Yang et al.), one on an amphenicol antibiotic, florfenicol (Rairat et al.), and one on a non-steroidal anti-inflammatory drug (NSAID), meloxicam (Moron-Elorza et al.). Concerned species include crucian carp (Carassius auratus gibelio), yellow river carp (Cyprinus carpio haematoperus), Nile tilapia (Oreochromis niloticus), and large-spotted catsharks (Scyliorhinus stellaris). The lone non-pharmacokinetic submission was about the evaluation of the anti-oomycete activity of chlorhexidine gluconate against Saprolegnia spp. through molecular docking, in silico analysis, and determination of minimum inhibitory/fungicidal concentrations (Thakuria et al.). An interesting observation is that the second edition's content is exactly the same as in the first edition, where five of the six articles were related to pharmacokinetic research. Aside from possible influences from the editors' background, the collection of articles might again reflect the lack of clinical instruction on limited pharmaceutics available for aquatic species and the need to resolve these shortcomings. Therefore, it might be worthwhile to cast a deeper look into the unique features of pharmacokinetics in aquatic species, mainly fish, as they represent the main body of the two editions of aquatic pharmacology.
Pharmacokinetic studies can give rise to information critical for determining of dose, dosing interval, drug-drug interactions, and in food animals, the withdrawal times to assure efficient treatment and safeguard food from residual toxicity to humans. Such information should be tailored to matched animal species and drugs under specified conditions. This is especially true and even more critical for aquatic animals. Using farm fish as an example, spread-dosing with feed in their rearing environment renders higher dose variation. Drugs, either in parent or metabolized forms, stay in the environment where fish live, creating a continuous immersion effect and could further pollute their living environment and intoxicate surrounding non-target organisms. This creates a unique concern/feature for approval of medicines in aquatic species because risks associated with inappropriate uses, explicitly tissue residue violations, drug resistance, and environmental pollution, could be well above those in land animals. Furthermore, as fish are poikilothermic animals, their body temperature and metabolic rate fundamentally depend on water temperature. An increase in water temperature would result in increased metabolic rate, blood flow (and blood flow-dependent clearance), and drug-metabolizing enzyme activity; such that the pharmacokinetic behaviors of aquatic medications are largely dictated by rearing temperatures. This temperature-dependent pharmacokinetics warrants specification of the temperature in order to formulate a more accurate optimal dosage. To make matters worse, aquatic species are very diversified. Currently, the pharmacokinetic information in use is mainly derived from a few representative fish in the same “order” rather than direct study of specific species, which adds further imprecision to the pharmacokinetic aspects of clinical practice.
Consequently, approved medications for aquatic species are significantly falling behind terrestrial animals. Again, using antibacterials approved for fish as an example, approved numbers of antibiotics in most countries are below twenty; for instance, only 1 in Norway (1), 3 in the USA (2), 6 in China (3), 11 in Thailand (4), 12 in Japan (5), and 14 in Taiwan (6). The European Union has the most approvals of 29 antibiotics (7) due to diversified territorial backgrounds encompassing more than 25 union countries with their preferred regulations. Antibiotics approved by most countries include florfenicol, oxytetracycline, sulfonamides, oxolinic acid, and amoxicillin. This factual scenario highlights the hardship of the effective use of available drugs for infection control in fish.
In addition to antibacterials, published aquatic pharmacokinetic research also mainly concentrates on anti-infectives, including anthelmintics (8–10), antivirals (11, 12), and natural botanic products with anti-infective peroperties (13–15). Drugs relating to experimental or medical management of aquatic species such as NSAIDs (16–18) and anesthetics (19–21) are also topics for pharmacokinetic studies. The majority of fish species include those of economic importance, such as carp, Nile tilapia, catfish, rainbow trout, Atlantic salmon, gilthead seabream, European seabass, and grouper (22). Other non-fish species that are also covered include shrimp (23, 24), crab (25, 26), frog (27, 28), turtle (29, 30), and crocodile (31), which also to some extent carry economic implications. Although it doesn't have to go far to find some publications related to aquatic pharmacokinetics, the lack of knowledge in need is no doubt significant.
On the other hand, it is notable that other than traditional pharmacokinetic studies concerning drug bioavailability, tissue distribution, enzymes metabolism, withdrawal times, and factors affecting (ex. temperature and salinity) those processes, the population pharmacokinetics was also seen in this edition. Population pharmacokinetic studies evaluate drug disposition features in a population, using a limited number of samples per study subject and considering the influence of diverse clinical/pathophysiological factors and individual variability on pharmacokinetics. It can be a tool to optimize the determination of efficacy and safety of drugs. The application of this methodology allows the establishment of withdrawal intervals tailored to the clinical or production conditions of populations or individuals such that a safer food supply is more likely for a wide variety of dose and off-label clinical uses (32). This approach is a delightful welcome that could bolster the benefit of pharmacokinetic research at reduced cost and labor.
As indicated in our first editorial, out of more than 300 veterinary and aquatic science journals listed in the science citation index (SCI), no single journal is dedicated specifically to pharmacological research in the aquatic species, not to mention any specialization in pharmacokinetics. While such journal is a far reach even for land animals, we hope the completion of this special topic edition could provoke the idea for a future journal section dedicated to the collection of articles pertaining to aquatic pharmacokinetics in the Frontiers in Veterinary Science-Veterinary Pharmacology and Toxicology.
Author contributions
All authors have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
Acknowledgments
The authors thank Dr. Tirawat Rairat at the Department of Fishery Biology, Faculty of Fisheries, Kasetsart University, for his contribution in literature summaries.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Norwegian Medicines Agency,. Pharmaceuticals for Fish, Holding Marketing Authorisation in Norway. Norwegian Medicines Agency (2022). Available online at: https://legemiddelverket.no/english/veterinary-medicine/fish-medicine-information-in-english
2. U.S. Food and Drug Administration. Approved Aquaculture Drugs. (2022). Available online at: https://www.fda.gov/animal-veterinary/aquaculture/approved-aquaculture-drugs
3. Ministry of Agriculture. Guideline of Fishery Drug Application (NY 5071-2002). Ministry of Agriculture [in Chinese] (2002). Available online at: http://hdl.handle.net/1834/32471
4. Thai FDA,. Restrictions on Antimicrobial Use in Aquaculture. Food Drug Administration, Ministry of Public Health [in Thai] (2012). Available online at: https://www4.fisheries.go.th/doffile/fkey/ref528
5. Ministry Ministry of Agriculture Forestry Fisheries. The Use of Aquatic Medicine, 35rd Report. Ministry of Agriculture, Forestry and Fisheries [in Japanese] (2022). Available online at: https://www.maff.go.jp/j/syouan/suisan/suisan_yobo/fishmed.html
6. Council of Agriculture. Guidelines for the Use of Animal Drugs Article 3 Annex I: Code of Practice for Aquatic Animal Drugs. Council of Agriculture (2022) [in Chinese]. Available online at: https://law.moj.gov.tw/LawClass/LawAll.aspx?pcode=M0130023
7. EC. Commission Regulation (EU) No 37/2010 of 22 December 2009 on Pharmacologically Active Substances and Their Classification Regarding Maximum Residue Limits in Foodstuffs of Animal Origin, 02010R0037-20220509. Official Journal of the European Union (2022). Available online at: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A02010R0037-20220509
8. Xu N, Dong J, Yang Y, Ai X. Pharmacokinetics and residue depletion of praziquantel in rice field eels Monopterus albus. Dis Aquat Organ. (2016) 119:67–74. doi: 10.3354/dao02979
9. Sadati NY, Youssefi MR, Hosseinifard SM, Tabari MA, Giorgi M. Pharmacokinetics and pharmacodynamics of single and multiple-dose levamisole in belugas (Huso huso): main focus on immunity responses. Fish Shellfish Immunol. (2021) 114:152–60. doi: 10.1016/j.fsi.2021.04.016
10. Men L, Zhang Y, Li K, Li Z, Li C, Zhang X, et al. Metabolism and pharmacokinetics of mebendazole in Japanese pufferfish (Takifugu rubripes). Food Addit Contam A. (2022) 39:912–24. doi: 10.1080/19440049.2022.2052974
11. Liu W, Xu J, Zhou Y, Chen J, Ma J, Zeng L. Pharmacokinetics and tissue residues of moroxydine hydrochloride in gibel carp, Carassius gibelio after oral administration. J Vet Pharmacol Ther. (2016) 39:398–404. doi: 10.1111/jvp.12289
12. Quijano Cardé EM, Yazdi Z, Yun S, Hu R, Knych H, Imai DM, et al. Pharmacokinetic and efficacy study of acyclovir against cyprinid herpesvirus 3 in Cyprinus carpio. Front Vet Sci. (2020) 7:587952. doi: 10.3389/fvets.2020.587952
13. Ling F, Wu ZQ, Jiang C, Liu L, Wang GX. Antibacterial efficacy and pharmacokinetic evaluation of sanguinarine in common carp (Cyprinus carpio) following a single intraperitoneal administration. J Fish Dis. (2016) 39:993–1000. doi: 10.1111/jfd.12433
14. Zoral MA, Ishikawa Y, Ohshima T, Futami K, Endo M, Maita M, et al. Toxicological effects and pharmacokinetics of rosemary (Rosmarinus officinalis) extract in common carp (Cyprinus carpio). Aquaculture. (2018) 495:955–60. doi: 10.1016/j.aquaculture.2018.06.048
15. Zhang Z, Cui H, Zhang Z, Qu S, Wang G, Ling F. Pharmacokinetics of magnolol following different routes of administration to goldfish (Carassius auratus) and its oral efficacy against Ichthyophthirius multififiliis infection. Aquaculture. (2022) 546:737356. doi: 10.1016/j.aquaculture.2021.737356
16. Martin M, Smith S, Kleinhenz M, Magnin G, Lin Z, Kuhn D, et al. Comparative pharmacokinetics and tissue concentrations of flunixin meglumine and meloxicam in tilapia (Oreochromis spp.). Fishes. (2021) 6:68. doi: 10.3390/fishes6040068
17. Raulic J, Beaudry F, Beauchamp G, Jalenques M, Summa N, Lair S, et al. Pharmacokinetic, pharmacodynamic, and toxicology study of robenacoxib in rainbow trout (Oncorhynchus mykiss). J Zoo Wildl Med. (2021) 52:529–37. doi: 10.1638/2020-0130
18. Uney K, Durna Corum D, Terzi E, Corum O. Pharmacokinetics and bioavailability of carprofen in rainbow trout (Oncorhynchus mykiss) broodstock. Pharmaceutics. (2021) 13:990. doi: 10.3390/pharmaceutics13070990
19. Oda A, Messenger KM, Carbajal L, Posner LP, Gardner BR, Hammer SH, et al. Pharmacokinetics and pharmacodynamic effects in koi carp (Cyprinus carpio) following immersion in propofol. Vet Anaesth Analg. (2018) 45:529–38. doi: 10.1016/j.vaa.2018.02.005
20. Tang Y, Zhang H, Yang G, Fang C, Kong C, Tian L, et al. Pharmacokinetics studies of eugenol in Pacific white shrimp (Litopenaeus vannamei) after immersion bath. BMC Vet Res. (2022) 18:122. doi: 10.1186/s12917-022-03145-3
21. Rairat T, Chi Y, Chang SK, Hsieh CY, Chuchird N, Chou CC. Differential effects of aquatic anesthetics on the pharmacokinetics of antibiotics: examples using florfenicol in Nile tilapia (Oreochromis niloticus). J Fish Dis. (2021) 44:1579–86. doi: 10.1111/jfd.13480
22. FAO. The State of World Fisheries and Aquaculture 2022. Food and Agriculture Organization of the United Nations (2022).
23. Feng Y, Zhai Q, Wang J, Li J, Li. J. Comparison of florfenicol pharmacokinetics in Exopalaemon carinicauda at different temperatures and administration routes. J Vet Pharmacol Ther. (2019) 42:230–8. doi: 10.1111/jvp.12734
24. Ma R, Wang Y, Zou X, Fu G, Li C, Fan P, et al. Pharmacokinetics of oxytetracycline in Pacific white shrimp, Penaeus vannamei, after oral administration of a single-dose and multiple-doses. Aquaculture. (2019) 512:734348. doi: 10.1016/j.aquaculture.2019.734348
25. Fu G, Peng J, Wang Y, Zhao S, Fang W, Hu K, et al. Pharmacokinetics and pharmacodynamics of sulfamethoxazole and trimethoprim in swimming crabs (Portunus trituberculatus) and in vitro antibacterial activity against Vibrio: PK/PD of SMZ-TMP in crabs and antibacterial activity against Vibrio. Environ Toxicol Pharmacol. (2016) 46:45–54. doi: 10.1016/j.etap.2016.06.029
26. Su H, Wei Y, Sun J, Hu K, Yang Z, Zheng R, et al. Effect of lactic acid on enrofloxacin pharmacokinetics in Eriocheir sinensis (Chinese mitten crab). Aquacult Res. (2019) 50:1040–6. doi: 10.1111/are.13976
27. Roberts AA, Berger L, Robertson SG, Webb RJ, Kosch TA, McFadden M, et al. The efficacy and pharmacokinetics of terbinafine against the frog-killing fungus (Batrachochytrium dendrobatidis). Med Mycol. (2019) 57:204–14. doi: 10.1093/mmy/myy010
28. Hawkins SJ, Cox SK, Sladky KK. Pharmacokinetics of ceftazidime in Northern leopard frogs (Lithobates pipiens) at two different doses and administration routes. Am J Vet Res. (2021) 82:560–5. doi: 10.2460/ajvr.82.7.560
29. Norton TM, Clauss T, Overmeyer R, Stowell S, Kaylor M, Cox S. Multi-injection pharmacokinetics of meloxicam in Kemp's Ridley (Lepidochelys kempii) and green (Chelonia mydas) sea turtles after subcutaneous administration. Animals. (2021) 11:3522. doi: 10.3390/ani11123522
30. Taylor E, Trott DJ, Kimble B, Xie S, Govendir M, McLelland DJ. Pharmacokinetic profile of a single dose of an oral pradofloxacin suspension administered to eastern long-necked turtles (Chelodina longicollis). J Vet Pharmacol Ther. (2021) 44:503–9. doi: 10.1111/jvp.12933
31. Poapolathep S, Klangkaew N, Wongwaipairoj T, Chaiyabutr N, Giorgi M, Poapolathep A. Pharmacokinetics of danofloxacin in freshwater crocodiles (Crocodylus siamensis) after intramuscular injection. J Vet Pharmacol Ther. (2022) 45:352–7. doi: 10.1111/jvp.13072
Keywords: pharmacokinetics, antibiotics, aquatic, anesthetics, anti-fungal, NSAIDs
Citation: Srisapoome P, Tell LA and Chou C-C (2022) Editorial: Aquatic Pharmacology, Volume II: Pharmacokinetics for Aquatic Species. Front. Vet. Sci. 9:1039868. doi: 10.3389/fvets.2022.1039868
Received: 08 September 2022; Accepted: 21 September 2022;
Published: 17 October 2022.
Edited and reviewed by: Arturo Anadón, Complutense University of Madrid, Spain
Copyright © 2022 Srisapoome, Tell and Chou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Chi-Chung Chou, ccchou@nchu.edu.tw