7d26259761f077168ea4d1cb6fb3cb87 pmc_9143053.pdf c747a09b023d5bf772bc69dd4854f8e64b5c3c25 pmc_9143053.pdf ecbe62019bd06cff3e60332e3d0a1907a1fc3c5dfb84bc595e849c8239e6b8af pmc_9143053.pdf Title: Swine as the Animal Model for Testing New Formulations of Anti-Inflammatory Drugs: Carprofen Pharmacokinetics and Bioavailability of the Intramuscular Route Subject: Carprofen (CP) is a non-steroidal anti-inflammatory drug (NSAID) frequently used to treat respiratory diseases in numerous small animals, but also in large species. CP is a formidable candidate for further therapeutic research of human inflammatory diseases using the pig as an animal model. However, CP administration in swine is very uncommon and respective pharmacokinetics/bioavailability studies are scarce. A simultaneous population pharmacokinetic analysis after CP intravenous and intramuscular administrations in pigs has shown high extent and rate of absorption and a similar distribution profile with respect to man and other mammals. However, clearance and half-life values found in swine suggest a slower elimination process than that observed in man and some other animal species. Although not reported in other species, liver and kidney concentrations achieved at 48 h post-intramuscular administration in pigs were ten times lower than those found in plasma. Simulations pointed to 4 mg/kg every 24 h as the best dosage regimen to achieve similar therapeutic levels to those observed in other animal species. All these findings support the use of pig as an animal model to study the anti-inflammatory effects of CP in humans. Keywords: population pharmacokinetics; tissue distribution; swine animal model; mass spectrometry; bioanalysis; carprofen; anti-inflammatory drugs Author: Lidia Gómez-Segura, Antoni Boix-Montañes, Mireia Mallandrich, Alexander Parra-Coca, José L. Soriano-Ruiz, Ana Cristina Calpena, Álvaro Gimeno, David Bellido and Helena Colom Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu May 12 08:34:09 2022 CEST ModDate: Thu May 12 08:39:40 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1979194 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MIDETX+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 XWBKRI+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 JYYBXE+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 UABPYD+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 IAFAOG+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 43 0 CQTSWU+EURM10 Type 1 Builtin yes yes no 71 0 LYVYPF+VnURWPalladioL Type 1 Custom yes yes no 78 0 OJYQXC+CMSY10 Type 1 Builtin yes yes no 82 0 AUPURT+EURM7 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WinAnsi yes yes no 220 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 224 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 246 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 250 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 254 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 258 0 SymbolMT CID TrueType Identity-H yes no yes 265 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-09-30 02:32:38 CEST RepresentationInformation: pmc_9143053.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-06-14 07:17:33 CEST Size: 1979194 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 495 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4923ab24 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: Animals and Chemicals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Experimental Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Liquid Chromatography-Mass Spectrometry Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Children: Item: Title: Standard Curve Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: LC-MS/MS Method Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Analytical Validation Assays Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Sample Preparation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Recovery from Liver and Kidney Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Pharmacokinetic Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Children: Item: Title: Non-Compartmental Pharmacokinetic Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Pharmacokinetic Modeling Using the Population Approach Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Model Development Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Model Evaluation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Simulations and Model Applicability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Children: Item: Title: Liquid Chromatography-Mass Spectrometry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Recovery from Liver and Kidney Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Carprofen Plasma/Tissue Concentrations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Carprofen Pharmacokinetic Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Children: Item: Title: Non-Compartmental Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Population Pharmacokinetic Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Simulations and Model Applicability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Info: Title: Swine as the Animal Model for Testing New Formulations of Anti-Inflammatory Drugs: Carprofen Pharmacokinetics and Bioavailability of the Intramuscular Route Author: Lidia Gómez-Segura, Antoni Boix-Montañes, Mireia Mallandrich, Alexander Parra-Coca, José L. Soriano-Ruiz, Ana Cristina Calpena, Álvaro Gimeno, David Bellido and Helena Colom Subject: Carprofen (CP) is a non-steroidal anti-inflammatory drug (NSAID) frequently used to treat respiratory diseases in numerous small animals, but also in large species. CP is a formidable candidate for further therapeutic research of human inflammatory diseases using the pig as an animal model. However, CP administration in swine is very uncommon and respective pharmacokinetics/bioavailability studies are scarce. A simultaneous population pharmacokinetic analysis after CP intravenous and intramuscular administrations in pigs has shown high extent and rate of absorption and a similar distribution profile with respect to man and other mammals. However, clearance and half-life values found in swine suggest a slower elimination process than that observed in man and some other animal species. Although not reported in other species, liver and kidney concentrations achieved at 48 h post-intramuscular administration in pigs were ten times lower than those found in plasma. Simulations pointed to 4 mg/kg every 24 h as the best dosage regimen to achieve similar therapeutic levels to those observed in other animal species. All these findings support the use of pig as an animal model to study the anti-inflammatory effects of CP in humans. 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