Apparent Toxicity of Ketoconazole for Tursiops truncatus during Treatment of Lobomycosis
IAAAM Archive
J. P. Schroeder, DVM
Naval Ocean Systems Center, Hawaii Laboratory, Kailua, Hawaii

A 216 kg, mature, male bottlenose dolphin, Tt-583, captured in the Indian River area of Florida, housed in an ocean pen in Hawaii since August, 1977, had skin lesions suggestive of Lobo's Disease in July 1982. This animal had been captured at the same time and place as another mature male that died of complications of Lobo's Disease in 1978. Lobomycosis was diagnosed in both animals from biopsies of the suspected lesions based on the presence of fungal cells of Loboa loboi.

Ketoconazole has apparently been successful in treating dolphins for Lobomycosis at dose levels of 18 mg of Ketoconazole/kg of body weight, (Dudok Van Heel et al., 1977), and Candidiasis at dose levels of 20 mg/kg of body weight. (Nakeeb et al., 1980) and was administered at these levels to Tt-583. He exhibited adverse reactions to Ketoconazole that indicated this dose level was too high. The manufacturers state that it is important to recognize that liver disorders may occur with Ketoconazole due to the possibility of idiosyncratic hepatocellular dysfunction. Liver toxicity was evidenced in this case by significant increases in Serum Glutamic Oxalacetic Transaminase (SGOT), Serum Pyruvic Transaminase (SGPT) and possibly Lactic Dehydrogenase (LDH), as demonstrated in the following table:

Parameters

Tt-583 2-yr mean

Standard deviation

Baseline: Treatment started

19 days of treatment

180 days of treatment

210 days of Treatment

SGOT mu/ml

161

56 (N=22)

171

2200

548

160

SGPT mu/ml

45

16.8(N=21)

17

522

75

30

LDH -mu/ml

423

57.4(N-20)

289

1800

471

344

All other blood parameters stayed within normal value ranges for dolphins.

Other adverse reactions included: (1) anorexia resulting in a drop in food intake from 10 kg of fish per day to zero on days nine and ten, (2) the appearance of typical pox-like lesions over most of the animal's body, and (3) a drop in collected sperm from 6,232 x 106 to zero within three days. Five months after the start of treatment, the gross appearance of the lesions was much improved and the inflammatory response, seen previously by light microscopy, was gone. Electron microscopy of a biopsy of a lesion, however, revealed budding Loboa loboi cells indicating the value of electron microscopy in monitoring this disease.

A higher dose level of Ketoconazole seems to be indicated. Initial therapy in this case should have been at a dose level of 4-7 mg/kg and increased gradually to 10-16 mg/kg or higher, depending on indications of the liver's adjustment to the drug and electron microscopy findings.

Speaker Information
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J. Pete Schroeder, DVM
NOSC
Kaneohe, HI


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