{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:59:37Z","timestamp":1760144377934,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["RS-2023-00240204"],"award-info":[{"award-number":["RS-2023-00240204"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Gentamicin, an aminoglycoside antibiotic, is a mixture of therapeutically active C1, C1a, C2 and other minor components. Despite its decades-long use in pigs and other species, its intramuscular (IM) pharmacokinetics\/pharmacodynamics (PKs\/PDs) are unknown in piglets. Furthermore, the PKs of many drugs differ between healthy and sick animals. Therefore, we investigated the PKs of gentamicin after a single IM dose (10 mg\/kg) in healthy piglets and piglets that were intranasally co-infected with Actinobacillus pleuropneumoniae and Pasteurella multocida (PM). The plasma concentrations were measured using validated liquid chromatography\/mass spectrometry. The gentamicin exposure was 36% lower based on the area under the plasma concentration\u2013time curve and 16% lower based on the maximum plasma concentration (Cmax) in the infected piglets compared to the healthy piglets, while it was eliminated faster (shorter half-life and larger clearance) in the infected piglets compared to the healthy piglets. The clearance and volume of distribution were the highest for the C1 component. C1, C1a and C2 accounted for 22\u201325%, 33\u201337% and 40\u201342% of the total gentamicin exposure, respectively. The PK\/PD target for the efficacy of aminoglycosides (Cmax\/minimum inhibitory concentration (MIC) &gt; 10) could be exceeded for PM, with a greater magnitude in the healthy piglets. We suggest integrating this PK information with antibiotic susceptibility data for other bacteria to make informed antibiotic and dosage regimen selections against piglet infections.<\/jats:p>","DOI":"10.3390\/antibiotics13040372","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T07:55:54Z","timestamp":1713426954000},"page":"372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative Pharmacokinetics of Gentamicin C1, C1a and C2 in Healthy and Infected Piglets"],"prefix":"10.3390","volume":"13","author":[{"given":"Eun-Young","family":"Kim","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, Institute for Veterinary Biomedical Science, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5239-3833","authenticated-orcid":false,"given":"Tae-Won","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elias Gebru","family":"Awji","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, Institute for Veterinary Biomedical Science, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8668-4508","authenticated-orcid":false,"given":"Eon-Bee","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, Institute for Veterinary Biomedical Science, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"},{"name":"Veterinary Drugs & Biologics Division, Animal and Plant Quarantine Agency, Ministry of Agriculture, Food and Rural Affairs, Gimcheon 39660, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8539-1087","authenticated-orcid":false,"given":"Seung-Chun","family":"Park","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, Institute for Veterinary Biomedical Science, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"},{"name":"Cardiovascular Research Institute, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1128\/AAC.44.6.1443-1447.2000","article-title":"Pharmacokinetics of gentamicin C1, C1a, and C2 in beagles after a single intravenous dose","volume":"44","author":"Isoherranen","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"615","DOI":"10.2746\/042516402776180160","article-title":"Pharmacokinetics of gentamicin C1, C1a and C2 in horses after single intravenous dose","volume":"34","author":"Steinman","year":"2002","journal-title":"Equine Vet. J."},{"key":"ref_3","first-page":"1218","article-title":"Comparative in vitro activity of gentamicin and other antibiotics against bacteria isolated from clinical samples from dogs, cats, horses and cattle","volume":"70","author":"Bachmann","year":"1975","journal-title":"Vet. Med. Small. Anim. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/ecosalplus.esp-0002-2018","article-title":"Aminoglycoside revival: Review of a historically important class of antimicrobials undergoing rejuvenation","volume":"8","author":"Serio","year":"2018","journal-title":"EcoSal Plus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1128\/mr.51.4.439-457.1987","article-title":"Bacterial uptake of aminoglycoside antibiotics","volume":"51","author":"Taber","year":"1987","journal-title":"Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1261\/rna.068460.118","article-title":"Roles of specific aminoglycoside-ribosome interactions in the inhibition of translation","volume":"25","author":"Ying","year":"2019","journal-title":"RNA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1093\/infdis\/149.4.605","article-title":"Nephrotoxicity of the constituents of gentamicin complex","volume":"149","author":"Kohlhepp","year":"1984","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"32423","DOI":"10.1073\/pnas.2013065117","article-title":"Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes","volume":"117","author":"Song","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bulman, Z.P., Cirz, R., Hildebrandt, D., Kane, T., Rosario, Z., Wlasichuk, K., Park, M., and Andrews, L.D. (2020). Unraveling the gentamicin drug product complexity reveals variation in microbiological activities and nephrotoxicity. Antimicrob. Agents Chemother., 64.","DOI":"10.1128\/AAC.00533-20"},{"key":"ref_10","first-page":"129","article-title":"Pharmacokinetics of gentamicin C1, C1a, C2 and C2a in broiler chickens after IV, IM, SC and oral administration","volume":"5","author":"Gehring","year":"2013","journal-title":"J. Bioequiv. Availab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jchromb.2018.07.011","article-title":"Determination of gentamicin C components in fish tissues through SPE-Hypercarb-HPLC-MS\/MS","volume":"1093\u20131094","author":"Sun","year":"2018","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_12","first-page":"495","article-title":"Comparative pharmacokinetics of gentamicin in laying hens","volume":"19","author":"Filazi","year":"2013","journal-title":"Kafkas Univ. Vet. Fak. Derg."},{"key":"ref_13","first-page":"603","article-title":"Pharmacokinetics of gentamicin in cats given Escherichia coli endotoxin","volume":"49","author":"Jernigan","year":"1988","journal-title":"Am. J. Vet. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1365-2885.1995.tb00617.x","article-title":"Gentamicin pharmacokinetics in newborn and 42-day-old male piglets","volume":"18","author":"Giroux","year":"1995","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_15","first-page":"69","article-title":"Single intravenous and multiple intramuscular dose pharmacokinetics and tissue residue profile of gentamicin in sheep","volume":"46","author":"Brown","year":"1985","journal-title":"Am. J. Vet. Res."},{"key":"ref_16","first-page":"2461","article-title":"Pharmacokinetics of gentamicin in the calf: Developmental changes","volume":"46","author":"Clarke","year":"1985","journal-title":"Am. J. Vet. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1365-2885.1991.tb00845.x","article-title":"Disposition kinetics of gentamicin in buffalo calves (Bubalus bubalis) following single intravenous administration","volume":"14","author":"Garg","year":"1991","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1517\/17425255.1.4.629","article-title":"Regulation of drug metabolism and disposition during inflammation and infection Expert","volume":"1","author":"Renton","year":"2005","journal-title":"Opin. Drug. Metab. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1055\/a-1403-1976","article-title":"The porcine respiratory disease complex (PRDC)\u2014A clinical review","volume":"49","author":"Eddicks","year":"2021","journal-title":"Tierarztl. Prax. Ausg. G Grosstiere Nutztiere"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"283","DOI":"10.4142\/jvs.2017.18.3.283","article-title":"Survey of porcine respiratory disease complex-associated pathogens among commercial pig farms in Korea via oral fluid method","volume":"18","author":"Cheong","year":"2017","journal-title":"J. Vet. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jiac.2015.02.001","article-title":"Applications of the pharmacokinetic\/pharmacodynamic (PK\/PD) analysis of antimicrobial agents","volume":"21","author":"Isla","year":"2015","journal-title":"J. Infect. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1128\/AAC.05360-11","article-title":"Dosing regimen matters: The importance of early intervention and rapid attainment of the pharmacokinetic\/pharmacodynamic target","volume":"56","author":"Martinez","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kim, J., Kim, J.W., Oh, S.I., So, B., Kim, W.I., and Kim, H.Y. (2019). Characterisation of Pasteurella multocida isolates from pigs with pneumonia in Korea. BMC Vet. Res., 15.","DOI":"10.1186\/s12917-019-1861-5"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e000293","DOI":"10.1136\/vetreco-2018-000293","article-title":"Antimicrobial resistance of Pasteurella multocida strains isolated from pigs between 2010 and 2016","volume":"5","author":"Oh","year":"2018","journal-title":"Vet. Rec."},{"key":"ref_25","first-page":"89","article-title":"Gentamicin for the prevention and treatment of colibacillosis in piglets","volume":"74","author":"Ensley","year":"1979","journal-title":"Vet. Med. Small Anim. Clin."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1124\/dmd.120.090704","article-title":"The impact of infection and inflammation on drug metabolism, active transport, and systemic drug concentrations in veterinary species","volume":"48","author":"Martinez","year":"2020","journal-title":"Drug. Metab. Dispos."},{"key":"ref_27","first-page":"e61","article-title":"Assessment and comparison of bacterial load levels determined by quantitative amplifications in blood culture-positive and negative neonatal sepsis","volume":"25","author":"Stranieri","year":"2018","journal-title":"Rev. Inst. Med. Trop. S\u00e3o Paulo"},{"key":"ref_28","first-page":"e3210","article-title":"Genetic Predisposition to Infectious Disease","volume":"10","author":"Klebanov","year":"2018","journal-title":"Cureus"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"91","DOI":"10.5334\/aogh.3670","article-title":"Environmental Impacts on Infectious Disease: A Literature View of Epidemiological Evidence","volume":"88","author":"Sly","year":"2022","journal-title":"Ann. Glob. Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13567-020-0741-0","article-title":"Primary characterization of the immune response in pigs infected with Trichinella spiralis","volume":"51","author":"Wang","year":"2020","journal-title":"Vet. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e02613","DOI":"10.1002\/ecy.2613","article-title":"Individual and temporal variation in pathogen load predicts long-term impacts of an emerging infectious disease","volume":"100","author":"Wells","year":"2019","journal-title":"Ecology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1016\/j.jchromb.2008.09.030","article-title":"Key aspects of analytical method validation and linearity evaluation","volume":"877","author":"Araujo","year":"2009","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/bs.acc.2019.01.006","article-title":"A practical guide to validation and verification of analytical methods in the clinical laboratory","volume":"90","author":"Pum","year":"2019","journal-title":"Adv. Clin. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.talanta.2013.10.061","article-title":"Strategy for determination of LOD and LOQ values\u2013Some basic aspects","volume":"119","year":"2014","journal-title":"Talanta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5691","DOI":"10.1021\/acs.jmedchem.5b00201","article-title":"Volume of distribution in drug design","volume":"58","author":"Smith","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41421-020-00233-2","article-title":"Plasma membrane integrity in health and disease: Significance and therapeutic potential","volume":"7","author":"Dias","year":"2021","journal-title":"Cell Discov."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1258403","DOI":"10.3389\/fphar.2023.1258403","article-title":"Optimizing tylosin dosage for co-infection of Actinobacillus pleuropneumoniae and Pasteurella multocida in pigs using pharmacokinetic\/pharmacodynamic modeling","volume":"14","author":"Lee","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0378-1135(00)00345-X","article-title":"Identification and detection of Actinobacillus pleuropneumoniae by PCR based on the gene apxIVA","volume":"79","author":"Schaller","year":"2001","journal-title":"Vet. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6153","DOI":"10.1007\/s00203-021-02579-x","article-title":"Virulence attitude estimation of Pasteurella multocida isolates in embryonated chicken eggs","volume":"203","author":"Shalaby","year":"2021","journal-title":"Arch. Microbiol."},{"key":"ref_40","unstructured":"(2015, October 04). List of the Names, Pharmaceutical Forms, Strengths of the Veterinary Medicinal Products, Animal Species, Applicants\/Marketing Authorisation Holders in the Member States. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/referral\/gentamicin-article-35-veterinary-medicinal-products-containing-gentamicin-presented-solutions-injection-be-administered-horses-annex-i-ii-iii_en.pdf."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jchromb.2014.01.035","article-title":"A simple quantitative method analysing amikacin, gentamicin, and vancomycin levels in human newborn plasma using ion-pair liquid chromatography\/tandem mass spectrometry and its applicability to a clinical study","volume":"951","author":"Bijleveld","year":"2014","journal-title":"J. Chromatogr. B"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Dos Santos, A.L.A., da Silva, A.C.C., Lizot, L.D.L.F., Schneider, A., Meireles, Y.F., Hahn, R.Z., Pagnussat, L.R., Nonnenmacher, J.L., Hahn, S.R., and Linden, R. (2022). Development and validation of an assay for the measurement of gentamicin concentrations in dried blood spots using UHPLC-MS\/MS. J. Pharm. Biomed. Anal., 208.","DOI":"10.1016\/j.jpba.2021.114448"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/4\/372\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:29:56Z","timestamp":1760106596000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/4\/372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,18]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["antibiotics13040372"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics13040372","relation":{},"ISSN":["2079-6382"],"issn-type":[{"type":"electronic","value":"2079-6382"}],"subject":[],"published":{"date-parts":[[2024,4,18]]}}}