Exploring the Pharmacokinetics of Phenoxymethylpenicillin (Penicillin-V) in Adults: A Healthy Volunteer Study

This healthy volunteer study aimed to explore phenoxymethylpenicillin (penicillin-V) pharmacokinetics (PK) to support the planning of large dosing studies in adults. Volunteers were dosed with penicillin-V at steady state. Total and unbound penicillin-V serum concentrations were determined, and a base population PK model was fitted to the data.

Feasibility of Upper Gastrointestinal Examination in Home Care Setting with a Magnetically Assisted Capsule Endoscopy System: A Retrospective Study

The magnetic assisted capsule endoscope (MACE) with a hand-held magnetic field navigator (MFN) for upper gastrointestinal examination achieved satisfactory results in a healthy volunteer study. We evaluated the feasibility of upper gastrointestinal examination in the home care setting with the MACE system. Home care patients with upper gastrointestinal symptoms that received an MACE exam were enrolled in the study. MACE procedure time; completeness of observation of important anatomical landmarks; endoscopic diagnosis; patient tolerance during the procedure; and patient data, including age, sex, comorbidities, symptoms, body weight, and height, were retrieved from hospital information system for data analysis. A total of 16 participants were enrolled with a mean age 74.3 ± 15.4 years (47 to 99 years). One patient failed to swallow the capsule and was excluded. The average procedure time was 23.7 ± 10.0 min (14.1 to 42.5 min) to complete each endoscopic exam for the remaining 15 patients. The overall maneuverability in the esophagus, stomach, and duodenum was 93.75%, 87.5%, and 75%, respectively. Overall completeness in the aforementioned regions was 93.75%, 81.25%, and 75%, respectively. No severe adverse events were noted. The results clearly demonstrate the promise of using this MACE system to perform endoscopic examination outside the hospital for patients confined to the community and home.

The Effects of Hypocapnia on Brain Tissue Pulsations

Hypocapnia is known to affect patients with acute stroke and plays a key role in governing cerebral autoregulation. However, the impact of hypocapnia on brain tissue pulsations (BTPs) is relatively unexplored. As BTPs are hypothesised to result from cerebrovascular resistance to the inflow of pulsatile arterial blood, it has also been hypothesised that cerebral autoregulation changes mediated by hypocapnia will alter BTP amplitude. This healthy volunteer study reports measurements of BTPs obtained using transcranial tissue Doppler (TCTD). Thirty participants underwent hyperventilation to induce mild hypocapnia. BTP amplitude, EtCO2, blood pressure, and heart rate were then analysed to explore the impact of hypocapnia on BTP amplitude. Significant changes in BTP amplitude were noted during recovery from hypocapnia, but not during the hyperventilation manoeuvre itself. However, a significant increase in heart rate and pulse pressure and decrease in mean arterial pressure were also observed to accompany hypocapnia, which may have confounded our findings. Whilst further investigation is required, the results of this study provide a starting point for better understanding of the effects of carbon dioxide levels on BTPs. Further research in this area is needed to identify the major physiological drivers of BTPs and quantify their interactions with other aspects of cerebral haemodynamics.

Concomitant limb cryocompression and scalp cooling to reduce paclitaxel-induced neuropathy and alopecia.

e24157 Background: Scalp cooling is an FDA approved method to mitigate chemotherapy-induced alopecia (CIA) caused by paclitaxel. Chemotherapy-induced peripheral neuropathy (CIPN) is a dose limiting toxicity of paclitaxel. Several recent randomized studies have suggested limb hypothermia as a mechanism to ameliorate paclitaxel-induced neuropathy. The safety, tolerability and feasibility of concomitant limb hypothermia and scalp cooling to prevent these two common adverse effects of paclitaxel has not been previously studied. Methods: A proof-of-concept study was conducted in breast cancer patients receiving weekly paclitaxel chemotherapy. Each subject underwent concomitant scalp and four-limb cryocompression with each chemotherapy infusion (3 hours) for a maximum of 12 cycles. Limb cryocompression was administered at cyclic pressure (5-15 mmHg) and temperatures starting at 11°C (established as lowest tolerable temperature in a separate healthy volunteer study) and adjusted according to patient tolerability. Skin surface temperature and tolerance scores were recorded. CIPN was assessed via EORTC Quality of Life Questionnaire-CIPN before (QOLpre), after completion (QOLpost) and 3-months post chemotherapy (QOL3m). Results: Fifteen patients enrolled in the study, of which 14 completed all 12 cycles of concomitant scalp cooling and limb cryocompression during chemotherapy without any side effects barring transient erythema over the limbs. None had intolerance to scalp cooling. Eight patients safely tolerated 12 cycles of cryocompression at 11°C. Of the remaining, 6 completed all 12 cycles at device temperatures ranging from 14-25°C. One patient withdrew at the 6th cycle, finding 25°C intolerable. Median QOLpre was 19 (range 17-19), QOLpost 20 (18-29) (p = 0.04, Wilcoxon signed-rank) and QOL3m was 19 (18-21) (vs QOLpre; p = 1). QOL showed no significant differences from pre-chemotherapy to 3 months post-chemotherapy suggesting preservation of nerve function. Conclusions: Delivery of concomitant scalp cooling and limb cryocompression is feasible, safe and generally well-tolerated. Future limb hypothermia trials should not preclude patients from undergoing scalp-cooling concomitantly to reduce CIA. Clinical trial information: NCT03248193 .

1578. Rifampicin Reduces Tedizolid Concentrations When Co-Administered in Healthy Volunteers

Background Tedizolid is an oxazolidinone used to treat skin and soft-tissue infections. Rifampicin is a rifamycin antibiotic which can also treat skin and soft-tissue infections, such as those caused by Staphylococcus aureus. Tedizolid and rifampicin could be therefore used concurrently to treat infections. There is currently no clinical data on whether rifampicin affects tedizolid concentrations. Rifampicin is known to be an inducer of cytochrome P450s and transporters. Tedizolid is not known to be cleared by cytochrome P450s, but could be affected by other clearance mechanisms. Therefore we conducted a pharmacokinetic drug-drug interaction study to investigate whether 2 weeks of rifampicin can affect tedizolid concentrations. Methods We conducted a healthy volunteer study in 8 subjects. Subjects were first given linezolid 600 mg on day 1, tedizolid 200 mg on day 4, rifampicin 600 mg daily from days 5 to 19 (2 weeks of rifampicin), and an additional dose of tedizolid 200 mg on day 19. Blood was obtained at pre-dose, 1, 2, 3, 4, 5, 6, 8, and 24 hours post dose on days 4 and 19. Concentrations of tedizolid were measured using a validated liquid chromatography / mass spectrometry method. Pharmacokinetic parameters were calculated by Non-Compartmental Analyses using Phoenix WinNonLin version 8.0. The bioequivalence module was used to obtain ratios of PK parameters pre- and post-rifampicin. Results Eight subjects were included in the study. Median age (range) and weight were 34.5 (29–44) years and 64 (58.4–90.8) kg, respectively. Tedizolid was well tolerated in the study. Tedizolid AUC (0–24 hours) was reduced after 2 weeks of rifampicin (GMR 0.80, 90% confidence interval 0.73–0.88), as was Cmin (0.54, 0.44–0.66) and Cmax (0.85, 0.79–0.91). Clearance/F of tedizolid was significantly increased after rifampicin (1.35, 1.21–1.50). Conclusion Rifampicin given for 2 weeks has the potential to reduce tedizolid concentrations, especially trough levels, which was reduced by 46%. Caution is recommended when using tedizolid together with rifampicin, especially when tedizolid MIC is high or treating difficult infections. Disclosures All authors: No reported disclosures.