Penicillin concentrations in oropharyngeal and frontal sinus tissue following enteral and intravenous administration measured by microdialysis in a porcine model

Pelle Hanberg; Hans Christian Rasmussen; Mats Bue; Maiken Stilling; Andrea René Jørgensen; Elisabeth Krogsgaard Petersen; Johanne Gade Lilleøre; Magnus A. Hvistendahl; Jesper Bille; Tejs Ehlers Klug

doi:10.1016/j.ejps.2024.106859

Penicillin concentrations in oropharyngeal and frontal sinus tissue following enteral and intravenous administration measured by microdialysis in a porcine model

Pelle Hanberg^*, Hans Christian Rasmussen, Mats Bue, Maiken Stilling, Andrea René Jørgensen, Elisabeth Krogsgaard Petersen, Johanne Gade Lilleøre, Magnus A. Hvistendahl, Jesper Bille, Tejs Ehlers Klug

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

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: 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: 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: 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.

Original language	English
Article number	106859
Journal	European Journal of Pharmaceutical Sciences
Volume	201
ISSN	0928-0987
DOIs	https://doi.org/10.1016/j.ejps.2024.106859
Publication status	Published - Oct 2024

Keywords

Antimicrobial
Frontal sinus tissue
Oropharyngeal tissue
Penicillin
Pharmacokinetics

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10.1016/j.ejps.2024.106859Licence: CC BY

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Hanberg, P., Rasmussen, H. C., Bue, M., Stilling, M., Jørgensen, A. R., Petersen, E. K., Lilleøre, J. G., Hvistendahl, M. A., Bille, J., & Klug, T. E. (2024). Penicillin concentrations in oropharyngeal and frontal sinus tissue following enteral and intravenous administration measured by microdialysis in a porcine model. European Journal of Pharmaceutical Sciences, 201, Article 106859. https://doi.org/10.1016/j.ejps.2024.106859

@article{f806138e3d5245ffaecb84dea8ca41a7,

title = "Penicillin concentrations in oropharyngeal and frontal sinus tissue following enteral and intravenous administration measured by microdialysis in a porcine model",

abstract = "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: 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: 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: 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.",

keywords = "Antimicrobial, Frontal sinus tissue, Oropharyngeal tissue, Penicillin, Pharmacokinetics",

author = "Pelle Hanberg and Rasmussen, {Hans Christian} and Mats Bue and Maiken Stilling and J{\o}rgensen, {Andrea Ren{\'e}} and Petersen, {Elisabeth Krogsgaard} and Lille{\o}re, {Johanne Gade} and Hvistendahl, {Magnus A.} and Jesper Bille and Klug, {Tejs Ehlers}",

year = "2024",

month = oct,

doi = "10.1016/j.ejps.2024.106859",

language = "English",

volume = "201",

journal = "European Journal of Pharmaceutical Sciences",

issn = "0928-0987",

publisher = "Elsevier B.V.",

}

Hanberg, P , Rasmussen, HC , Bue, M , Stilling, M , Jørgensen, AR , Petersen, EK , Lilleøre, JG , Hvistendahl, MA , Bille, J & Klug, TE 2024, 'Penicillin concentrations in oropharyngeal and frontal sinus tissue following enteral and intravenous administration measured by microdialysis in a porcine model', European Journal of Pharmaceutical Sciences, vol. 201, 106859. https://doi.org/10.1016/j.ejps.2024.106859

Penicillin concentrations in oropharyngeal and frontal sinus tissue following enteral and intravenous administration measured by microdialysis in a porcine model. / Hanberg, Pelle ; Rasmussen, Hans Christian ; Bue, Mats et al.
In: European Journal of Pharmaceutical Sciences, Vol. 201, 106859, 10.2024.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Penicillin concentrations in oropharyngeal and frontal sinus tissue following enteral and intravenous administration measured by microdialysis in a porcine model

AU - Hanberg, Pelle

AU - Rasmussen, Hans Christian

AU - Bue, Mats

AU - Stilling, Maiken

AU - Jørgensen, Andrea René

AU - Petersen, Elisabeth Krogsgaard

AU - Lilleøre, Johanne Gade

AU - Hvistendahl, Magnus A.

AU - Bille, Jesper

AU - Klug, Tejs Ehlers

PY - 2024/10

Y1 - 2024/10

N2 - 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: 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: 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: 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.

AB - 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: 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: 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: 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.

KW - Antimicrobial

KW - Frontal sinus tissue

KW - Oropharyngeal tissue

KW - Penicillin

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=85199516125&partnerID=8YFLogxK

U2 - 10.1016/j.ejps.2024.106859

DO - 10.1016/j.ejps.2024.106859

M3 - Journal article

C2 - 39038689

AN - SCOPUS:85199516125

SN - 0928-0987

VL - 201

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

M1 - 106859

ER -

Penicillin concentrations in oropharyngeal and frontal sinus tissue following enteral and intravenous administration measured by microdialysis in a porcine model

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