Repeated Administration of Pharmaceutical-Grade Medium-Chain Triglycerides, a Common Pharmacologic Excipient, Confers Dose-Dependent Toxicity by the Intraperitoneal but Not Oral Route in Mice.

Abstract

Pharmaceutical-grade medium-chain triglycerides (MCTs) are common excipients for in vivo pharmacological studies in laboratory animals and as an experimental therapeutic in certain metabolic and neurologic disorders. In this study, we examined the tolerability of repeated administration of a pharmaceutical-grade formulation of 3 MCTs-caprylic, capric, and lauric acid-in mice via the oral and intraperitoneal routes. We administered either 8 or 4 µL of 100% MCTs or saline/gram of body weight (∼7.56 or 3.78 g/kg, respectively) twice daily for 7 d. During administration, and for 7 d after, we monitored weight change and clinical presentation. On day 14, or upon meeting euthanasia criteria, animals were sacrificed for gross necropsy, histology, and CBC. We observed significant weight loss, clinical decline, and 100% mortality in animals receiving 8 µL/g MCTs via the intraperitoneal route of administration. Gross necropsy revealed serosanguinous fluid in the thoracic cavity, dark red mottled lungs, and adhesions in the abdominal cavity. Histology confirmed inflammation of the lungs, mediastinum, and peritoneum. Mild pathology and initial weight loss (through day 3) were also present in mice receiving 4 µL/g MCTs IP. However, these animals regained weight by day 7 and exhibited no clinical decline or mortality. These adverse effects were not seen in animals receiving either 8 µL/g MCTs PO or 8 µL/g saline IP. These findings suggest that repeated intraperitoneal administration of MCTs may cause dose-dependent toxicity and mortality at high doses, but it confers no adverse effects when administered via the oral route.