Severe bradycardia and hypotension in anaesthetized pigs: Possible interaction between octreotide, xylazine, and atropine: A case series

Pigs are common animal models in diabetes research. Streptozotocin-induced destruction of pancreatic β-cells is used to induce diabetes in conscious pigs. However, in short-term non-recovery experiments, suppression of endogenous insulin secretion can be faster and more easily achieved with somatostatin analogues. We report a series of severe and unexpected episodes of severe bradycardia in eight pigs during non-recovery experiments with the original aim of investigating the pharmacokinetics and pharmacodynamics of intraperitoneal hormone delivery. The adverse events occurred four to five hours into the experiments, and we believe that they were caused by an interaction between the somatostatin analogue octreotide, and the sedative drug xylazine and that atropine delayed the time of occurrence

A Patient With Maculopapular Rash and Lichenoid Skin Damage Caused by Ponatinib

Tyrosine kinase inhibitors (TKIs) are invaluable for the treatment of patients with chronic myelogenous leukemia. Although TKIs are generally better tolerated than traditional chemotherapy, dermatologic side effects are common and present a significant cause of concern for both patients and physicians. Ponatinib is a third-generation TKI and the only kinase inhibitor effective in patients with certain BCR-ABL1 mutations, including the T315I mutation. However, ponatinib is associated with an increased risk of serious side effects, and severe cutaneous reactions have increasingly been reported. We present a patient who developed a cutaneous lichenoid eruption following the initiation of ponatinib, which resolved after treatment with a topical retinoid. This case demonstrates that cutaneous side effects caused by ponatinib can be managed relatively easily, allowing patients to continue treatment with ponatinib. This is important considerting the limited alternative treatment approaches available for BCR-ABL1 T315I chronic myelogenous leukemia

Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism

Background and Objective Artificial pancreases administering low-dose glucagon in addition to insulin have the scope to improve glucose control in patients with diabetes mellitus type 1. If such a device were to deliver both hormones intraperitoneally, it would mimic normal physiology, which may be beneficial. However, the pharmacokinetic properties of glucagon after intraperitoneal administration are not well known. Hence, the current study aims to evaluate the relationship between the amount of intraperitoneally delivered glucagon and pharmacokinetic variables in a pig model. Methods Pharmacokinetic data was retrieved from experiments on 19 anaesthetised pigs and analysed post hoc. The animals received a single intraperitoneal bolus of glucagon ranging from 0.30 to 4.46 µg/kg. Plasma glucagon was measured every 2–10 min for 50 min. Results Peak plasma concentration and area under the time–plasma concentration curve of glucagon correlated positively with the administered dose, and larger boluses provided a relatively greater increase. The mean (standard deviation) time to maximum glucagon concentration in plasma was 11 (5) min, and the mean elimination half-life of glucagon in plasma was 19 (7) min. Conclusions Maximum plasma concentration and area under the time–plasma concentration curve of glucagon increase nonlinearly in relation to the intraperitoneally administered glucagon dose. We hypothesise that the results are compatible with a satiable first-pass metabolism in the liver. Time to maximum glucagon concentration in plasma and the elimination half-life of glucagon in plasma seem independent of the drug dose