Case Description—A 2-year-old spayed female Border Collie was treated with IV lipid emulsion (ILE) after ingesting 6 mg/kg (2.73 mg/lb) of an equine ivermectin anthelmintic paste 8 hours prior to examination.
Clinical Findings—On initial examination, the dog had stable cardiovascular signs but had diffuse muscle tremors and was hyperthermic. Neurologic evaluation revealed that the dog was ataxic and had mydriasis with bilaterally absent menace responses and pupillary light reflexes. The remaining physical examination findings were unremarkable. Results of CBC, serum biochemical analysis, venous blood gas analysis, and measurement of plasma lactate concentration were also within reference limits.
Treatment and Outcome—The dog was treated with ILE in addition to supportive care with IV fluid therapy and cardiovascular, respiratory, and neurologic monitoring. The use of ILE treatment was initiated in this patient on the basis of previous clinical and experimental evidence supporting its use for toxicosis resulting from lipid-soluble agents. An initial bolus of 1.5 mL/kg (0.68 mL/lb) of a 20% sterile lipid solution was administered IV over 10 minutes, followed by a constant rate infusion of 0.25 mL/kg/min (0.11 mL/lb/min) over 60 minutes that was administered twice to treat clinical signs of ivermectin toxicosis. The dog was discharged from the hospital 48 hours after admission and was clinically normal within 4 days after ivermectin ingestion. Further diagnostic evaluation subsequently revealed that this dog was unaffected by the multidrug resistance gene (MDR-1) deletion, known as the ATP-binding cassette polymorphism.
Clinical Relevance—Ivermectin toxicosis in veterinary patients can result in death without aggressive treatment, and severe toxicosis often requires mechanical ventilation and intensive supportive care. This is particularly true in dogs affected by the ATP-binding cassette polymorphism. Novel ILE treatment has been shown to be effective in human patients with lipid-soluble drug toxicoses, although the exact mechanism is unknown. In the patient in the present report, ILE was used successfully to treat ivermectin toxicosis, and results of serial measurement of serum ivermectin concentration supported the proposed lipid sink mechanism of action.
OBJECTIVE To characterize pharmacokinetics of cyclophosphamide and 4-hydoxycyclophosphamide (4-OHCP) in the plasma of healthy cats after oral, IV, and IP administration of cyclophosphamide.
ANIMALS 6 healthy adult cats.
PROCEDURES Cats were randomly assigned to receive cyclophosphamide (200 mg/m2) via each of 3 routes of administration (oral, IV, and IP); there was a 30-day washout period between successive treatments. Plasma samples were obtained at various time points for up to 8 hours after administration. Samples were treated with semicarbazide hydrochloride to trap the 4-OHCP in stable form, which allowed for cyclophosphamide and trapped 4-OHCP to be simultaneously measured by use of tandem mass spectrometry. Pharmacokinetic parameters were determined from drug concentration-versus-time data for both cyclophosphamide and 4-OHCP.
RESULTS Cyclophosphamide was tolerated well regardless of route of administration. Pharmacokinetic parameters for 4-OHCP were similar after oral, IV, and IP administration. Area under the concentration-time curve for cyclophosphamide was lower after oral administration than after IV or IP administration.
CONCLUSIONS AND CLINICAL RELEVANCE Cyclophosphamide can be administered interchangeably to cats as oral, IV, and IP formulations, which should provide benefits with regard to cost and ease of administration to certain feline patients.