TY - JOUR
T1 - Penicillin concentrations in bone and subcutaneous tissue: A porcine microdialysis study comparing oral and intravenous treatment
AU - Rasmussen, Hans Christian
AU - Hanberg, Pelle Emil
AU - Lilleøre, Johanne Gade
AU - Petersen, Elisabeth Krogsgaard
AU - Hvistendahl, Magnus A.
AU - Jørgensen, Andrea René
AU - Stilling, Maiken
AU - Bue, Mats
PY - 2024/12
Y1 - 2024/12
N2 - Penicillin is available in both an oral (penicillin V) and intravenous formulation (penicillin G), theoretically allowing for a safe transition between the two. However, the use of oral penicillin remains a topic of debate due to low and variable bioavailability. This study aimed to assess the time for which the free penicillin concentration exceeded targeted minimum inhibitory concentrations for Staphylococcus aureus and Streptococcus species (0.125, 0.25, and 0.5 mg/L) in cancellous bone and subcutaneous tissue after intravenous penicillin and oral penicillin administration. 12 female pigs (68–75 kg) were assigned, according to local standard clinical regimes, to either intravenous penicillin (1.2 g) or oral penicillin (0.8 g) treatment every 6 h over an 18 h period. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was dynamic/continually collected in the first dosing interval (0–6 h), simulating a prophylactic situation, and the third dosing interval (12–18 h), simulating a therapeutic setting. Plasma samples were collected for reference. For all investigated targets, intravenous treatment resulted in a longer mean time above relevant minimum inhibitory concentrations in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral treatment. With clinically relevant dosing, intravenous penicillin provides superior exposure compared to oral penicillin in both a prophylactic and therapeutic setting.
AB - Penicillin is available in both an oral (penicillin V) and intravenous formulation (penicillin G), theoretically allowing for a safe transition between the two. However, the use of oral penicillin remains a topic of debate due to low and variable bioavailability. This study aimed to assess the time for which the free penicillin concentration exceeded targeted minimum inhibitory concentrations for Staphylococcus aureus and Streptococcus species (0.125, 0.25, and 0.5 mg/L) in cancellous bone and subcutaneous tissue after intravenous penicillin and oral penicillin administration. 12 female pigs (68–75 kg) were assigned, according to local standard clinical regimes, to either intravenous penicillin (1.2 g) or oral penicillin (0.8 g) treatment every 6 h over an 18 h period. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was dynamic/continually collected in the first dosing interval (0–6 h), simulating a prophylactic situation, and the third dosing interval (12–18 h), simulating a therapeutic setting. Plasma samples were collected for reference. For all investigated targets, intravenous treatment resulted in a longer mean time above relevant minimum inhibitory concentrations in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral treatment. With clinically relevant dosing, intravenous penicillin provides superior exposure compared to oral penicillin in both a prophylactic and therapeutic setting.
KW - bone
KW - microdialysis
KW - penicillin G
KW - penicillin V
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85200335040&partnerID=8YFLogxK
U2 - 10.1002/jor.25947
DO - 10.1002/jor.25947
M3 - Journal article
C2 - 39101353
SN - 1554-527X
VL - 42
SP - 2844
EP - 2851
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 12
ER -