Penicillin concentrations in bone and subcutaneous tissue: A porcine microdialysis study comparing oral and intravenous treatment.

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.

Abdominal tissue concentrations and penetration of carboplatin in a HIPEC procedure ‒ assessment in a novel porcine model.

Objectives: Peritoneal dissemination from intraabdominal cancers is associated with poor prognosis and rapid disease progression. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an antineoplastic treatment, which has improved survival and recurrence-free survival, but little is known about the acquired chemotherapy concentrations in local tissues. The aim of this study was to assess concentrations of carboplatin during and after HIPEC treatment dynamically and simultaneously in various abdominal organ tissues by means of microdialysis in a novel porcine model. Methods: Eight pigs underwent imitation cytoreductive surgery followed by HIPEC (90 min) using a carboplatin dosage of 800 mg/m2. Microdialysis catheters were placed for sampling of drug concentrations in various solid tissues: peritoneum, liver, bladder wall, mesentery and in different depths of one mm and four mm in the hepatoduodenal ligament and rectum. During and after HIPEC, dialysates and blood samples were collected over 8 h. Results: No statistically significant differences in mean AUC0-last (range: 2,657-5,176 min·µg/mL), mean Cmax (range: 10.6-26.0 µg/mL) and mean Tmax (range: 105-206 min) were found between the compartments. In plasma there was a tendency towards lower measures. No difference between compartments was found for tissue penetration. At the last samples obtained (450 min) the mean carboplatin concentrations were 4.9-9.9 µg/mL across the investigated solid tissues. Conclusions: Equal carboplatin distribution in abdominal organ tissues, detectable concentrations for at least 6 h after HIPEC completion, and a carboplatin penetration depth of minimum four mm were found. The present study proposes a new HIPEC porcine model for future research.

Local Vancomycin Concentrations after Intra-articular Injection into the Knee Joint: An Experimental Porcine Study.

Intra-articular injection of vancomycin may be an important antimicrobial prophylactic supplement to systemic administration in the prevention of prosthetic joint infections. In eight female pigs, 500 mg of diluted vancomycin was given by intra-articular injection into the knee joint. Microdialysis was used for dense sampling of vancomycin concentrations over 12 hours in the synovial fluid of the knee joint, and in the adjacent femoral and tibial cancellous bone and subcutaneous tissue. Venous blood samples were obtained as reference. The mean (standard deviation [SD]) peak drug concentration of vancomycin in the synovial fluid of the knee joint was 5,277 (5,668) µg/mL. Only one pig failed to reach a peak drug concentration above 1,000 µg/mL. The concentration remained high throughout the sampling interval with a mean (SD) concentration of 337 (259) µg/mL after 690 minutes. For all extraarticular compartments, the pharmacokinetic parameters (area under the concentration time-curve, peak drug concentration, and time to peak drug concentration) were comparable. The highest extraarticular mean (SD) peak drug concentration of 4.4 (2.3) µg/mL was found in subcutaneous tissue. An intra-articular injection of 500 mg diluted vancomycin was found to provide significant prophylactic mean concentrations for at least 12 hours in the synovial fluid of the knee joint. Correspondingly, the adjacent tissue and plasma concentrations were low but remained stable, signifying low risk of systemic toxic side effects and a slow release or uptake from the synovium to the systemic circulation.