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
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
106859Informations de copyright
Copyright © 2024. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of competing interest None