Penicillin Concentrations in Oropharyngeal and Frontal Sinus Tissue Following Enteral and Intravenous Administration Measured by Microdialysis in a Porcine Model.

Antimicrobial Frontal sinus tissue Oropharyngeal tissue Penicillin Pharmacokinetics

Journal

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Titre abrégé: Eur J Pharm Sci
Pays: Netherlands
ID NLM: 9317982

Informations de publication

Date de publication:
20 Jul 2024
Historique:
received: 26 01 2024
revised: 08 04 2024
accepted: 19 07 2024
medline: 23 7 2024
pubmed: 23 7 2024
entrez: 22 7 2024
Statut: aheadofprint

Résumé

Penicillin may be administered enterally or intravenously for the treatment of bacterial infections within the oropharynx and the frontal sinuses. We aimed to assess and compare penicillin concentrations in oropharyngeal and frontal sinus tissues following enteral and intravenous administration in a porcine model. Twelve pigs were randomized to receive either enteral (0.8 g Penicillin V) or intravenous (1.2 g Penicillin G) penicillin. Microdialysis was used for sampling in oropharyngeal and frontal sinus tissues during a six-hour dosing interval. In addition, plasma samples were collected. The primary endpoints were time with drug concentration above the minimal inhibitory concentration (T>MIC) for two MIC targets: 0.125 (low target) and 0.5 (high target) μg/mL (covering Group A Streptococci, Fusobactarium necrophorum, Streptococcus pneumoniae and Hemophilus influenza) and attainment of these treatment targets for ≥50%T>MIC. For both the low and high MIC targets, intravenous administration resulted in higher T>MIC in oropharyngeal and frontal sinus tissues compared to enteral administration. In oropharyngeal tissue, the treatment target (≥50% T>MIC) was achieved for both the low target (96%) and high target (68%) when penicillin was administrated intravenously. In frontal sinus tissue, the treatment target was reached for the low target (70%), but not the high target (35%) when administered intravenously. None of the two tissues reached the treatment targets when penicillin was administered enterally. Intravenous administrated penicillin in standard dosage is superior to enteral administration of penicillin in standard dosage in achieving clinically important T>MIC as the majority of targets were achieved following intravenously administration, while none of the targets were achieved following enteral administration. These results support the general notion of higher tissue concentrations following intravenous compared to enteral administration.

Sections du résumé

BACKGROUND BACKGROUND
Penicillin may be administered enterally or intravenously for the treatment of bacterial infections within the oropharynx and the frontal sinuses. We aimed to assess and compare penicillin concentrations in oropharyngeal and frontal sinus tissues following enteral and intravenous administration in a porcine model.
METHOD METHODS
Twelve pigs were randomized to receive either enteral (0.8 g Penicillin V) or intravenous (1.2 g Penicillin G) penicillin. Microdialysis was used for sampling in oropharyngeal and frontal sinus tissues during a six-hour dosing interval. In addition, plasma samples were collected. The primary endpoints were time with drug concentration above the minimal inhibitory concentration (T>MIC) for two MIC targets: 0.125 (low target) and 0.5 (high target) μg/mL (covering Group A Streptococci, Fusobactarium necrophorum, Streptococcus pneumoniae and Hemophilus influenza) and attainment of these treatment targets for ≥50%T>MIC.
RESULTS RESULTS
For both the low and high MIC targets, intravenous administration resulted in higher T>MIC in oropharyngeal and frontal sinus tissues compared to enteral administration. In oropharyngeal tissue, the treatment target (≥50% T>MIC) was achieved for both the low target (96%) and high target (68%) when penicillin was administrated intravenously. In frontal sinus tissue, the treatment target was reached for the low target (70%), but not the high target (35%) when administered intravenously. None of the two tissues reached the treatment targets when penicillin was administered enterally.
CONCLUSION CONCLUSIONS
Intravenous administrated penicillin in standard dosage is superior to enteral administration of penicillin in standard dosage in achieving clinically important T>MIC as the majority of targets were achieved following intravenously administration, while none of the targets were achieved following enteral administration. These results support the general notion of higher tissue concentrations following intravenous compared to enteral administration.

Identifiants

pubmed: 39038689
pii: S0928-0987(24)00171-4
doi: 10.1016/j.ejps.2024.106859
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

106859

Informations de copyright

Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest None

Auteurs

Pelle Hanberg (P)

Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus Universitetshospital, FORUM, Palle Juul-Jensens Boulevard 11, 8200, Aarhus N, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus N, Denmark; Department of Otorhinolaryngology, Head and Neck Surgery, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark. Electronic address: pellehanberg@clin.au.dk.

Hans Christian Rasmussen (HC)

Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.

Mats Bue (M)

Department of Clinical Medicine, Aarhus Universitetshospital, FORUM, Palle Juul-Jensens Boulevard 11, 8200, Aarhus N, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.

Maiken Stilling (M)

Department of Clinical Medicine, Aarhus Universitetshospital, FORUM, Palle Juul-Jensens Boulevard 11, 8200, Aarhus N, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.

Andrea René Jørgensen (AR)

Department of Clinical Medicine, Aarhus Universitetshospital, FORUM, Palle Juul-Jensens Boulevard 11, 8200, Aarhus N, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus N, Denmark.

Elisabeth Krogsgaard Petersen (EK)

Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus N, Denmark.

Johanne Gade Lilleøre (JG)

Department of Clinical Medicine, Aarhus Universitetshospital, FORUM, Palle Juul-Jensens Boulevard 11, 8200, Aarhus N, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus N, Denmark.

Magnus A Hvistendahl (MA)

Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus N, Denmark.

Jesper Bille (J)

Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.

Tejs Ehlers Klug (TE)

Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus Universitetshospital, FORUM, Palle Juul-Jensens Boulevard 11, 8200, Aarhus N, Denmark.

Classifications MeSH