Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration

Aspergillosis is a condition causing serious morbidity and mortality in captive penguins and other bird species. It can be treated with antifungal drugs, such as voriconazole. However, the pharmacokinetics of voriconazole are variable between different animal and bird species. Therefore, the pharmacokinetics of voriconazole were investigated in this study in Magellanic penguins. Pharmacokinetic models were constructed and applied to predict the pharmacokinetics of voriconazole during long-term treatment in Magellanic penguins, since the voriconazole treatment duration in chronic aspergillosis cases can last up to several months. Plasma voriconazole concentration-time data from adult Magellanic penguins (Spheniscus magellanicus; n = 15) following a single oral (PO) dose of either 2.5 mg/kg or 5 mg/kg in a herring in three separate study periods 7-12 months apart were collected. Mean plasma voriconazole concentrations were above the targeted MIC for Aspergillus fumigatus for 2 hr following a single 2.5 mg/kg voriconazole dose while the plasma concentrations exceeded the MIC for least 24 hr following a 5 mg/kg dose. Nonlinear mixed-effects modeling was used to fit two pharmacokinetic models, one with first-order and another with saturable elimination, to the single-dose data. Fits were good for both, as long as dose was included as a covariate for the first-order model so that clearance was lower and the half-life longer for animals receiving the 5 mg/kg dose. Although the single-dose data suggested saturated elimination at higher concentrations, the model with saturable elimination did not predict plasma voriconazole concentrations well for a clinical aspergillosis case receiving long-term treatment, possibly because of induction of metabolizing enzymes with chronic exposure. Pharmacokinetic models should accurately predict plasma drug concentrations for different dosage regimens in order to be applicable in the field. Future studies should focus on determining clearance at steady-state to be able to refine the pharmacokinetic models presented here and improve model performance for long-term oral voriconazole administration in Magellanic penguins

Unusual splenic B-cell lymphoma in two related Sumatran tigers (Panthera tigris sumatrae)

Abstract CASE DESCRIPTION A 14-year-old 120-kg (264-lb) sexually intact male Sumatran tiger (Panthera tigris sumatrae) and its 10-year-old 130-kg (286-lb) sexually intact male offspring were housed separately and evaluated independently after experiencing weeks of ongoing malaise, weight loss, and anorexia. CLINICAL FINDINGS Both animals were immobilized and anesthetized for physical examinations and diagnostic testing. Complete blood counts revealed leukopenia and anemia in both tigers. Splenomegaly was identified on abdominal ultrasonography. Cytologic examination and immunohistochemical staining of splenic samples confirmed intermediate to large B-cell lymphoma; no evidence of lymphoma in surrounding organs was noted. TREATMENT AND OUTCOME The sire was treated with lomustine and prednisolone. This tiger was euthanized 21 months after initiation of treatment because of chronic progressive renal disease. The male offspring was treated with l-asparaginase but did not respond to the treatment. A splenectomy was performed, and malaise and anorexia resolved. No further chemotherapy was administered, and the male offspring was instead maintained on a low dose of prednisolone. Thirty-two months after diagnosis, the male offspring was still considered to be in remission. CLINICAL RELEVANCE To our knowledge, this was the first known report of the diagnosis and management of a splenic B-cell lymphoma in a tiger. Both tigers achieved positive clinical responses and long-term survival by means of different treatment modalities. The finding of such an unusual neoplasm in a male tiger and its male offspring was noteworthy, raising the possibility of a genetic predisposition for this lymphoma type. </jats:sec