Systemic availability of o,p’-ddd in normal dogs, fasted and fed, and in dogs with hyperadrenocorticism

Watson, A. D. J.; Rijnberk, A.; Moolenaar, A. J.

doi:10.1016/s0034-5288(18)30766-5

Cited by 31 publications

(17 citation statements)

References 15 publications

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“…Again, it has been suggested that absorption of mitotane is improved when given with food, especially a fatty meal. 16 In our study, we did not specify to pet owners to administer mitotane with meals to dogs, and that may have accounted for low absorption of the drug in at least some dogs. However, Simpson and Van Den Broek have demonstrated that intestinal fat absorption is increased in dogs with untreated PDH, and that fat absorption (and supposedly mitotane absorption) is reduced after treatment with mitotane."…”

Section: Discussionmentioning

confidence: 98%

Mitotane (o, p‘‐DDD) Treatment of 200 Dogs with Pituitary‐Dependent Hyperadrenocorticism

Kintzer

Peterson

1991

Veterinary Internal Medicne

117

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Two hundred dogs with pituitary dependent hyperadrenocorticism (PDH) were treated with mitotane a t an initial daily dosage of 21 to 69 mg/kg (mean = 45.2 mg/kg) for 5 to 14 days. During the induction period, 194 of the dogs also were given daily maintenance dosages of a glucocorticoid. Fifty of the dogs exhibited one or more adverse effects during initial induction, including weakness, vomiting, anorexia, diarrhea, and ataxia. After completion of the induction period, repeat ACTH stimulation testing revealed significant decreases in mean serum cortisol concentrations when compared with initial values. Twentyfive dogs, however, still responded to exogenous ACTH with serum cortisol concentrations above normal resting range, necessitating daily treatment for an additional 5 to 55 days. In contrast, 70 of the 200 dogs had low post-ACTH serum cortisol concentrations after the induction period. These subnormal serum cortisol concentrations generally increased spontaneously to within normal resting range 2 to 6 weeks after cessation of mitotane. In 184 dogs, mitotane was continued at an initial mean maintenance dosage of 49 mg/kg administered weekly in two to three divided doses. Of these dogs, 107 had one or more relapses of hyperadrenocorticism during treatment. In the 75 dogs that had one relapse, the median maintenance dosage was increased by approximately 35%, whereas the median maintenance dosage in the 32 dogs having two or more relapses was eventually increased by 225% over the initial dosage. After a mean maintenance treatment time of 2.0 years, the final maintenance dosage required in the 184 dogs ranged from 26.8 to 330 mg/kg/week. Concurrent glucocorticoid and mineralocorticoid deficiency (Addison's disease) developed in I1 dogs after 27 days to 3.5 years (median = 4.6 months) of maintenance mitotane. The mean survival time of the 200 dogs was 2.2 years (range = 10 days to 8.2 years). Of the 34 dogs that died or were euthanatized within the initial 6 months, 18 died because of complications of hyperadrenocorticism. In contrast, dogs usually did not die of complications associated with hyperadrenocorticism after the first few months of treatment, when the signs of disease were in remission. Eleven dogs died or were euthanatized as a result of the compressive effects of an expanding pituitary tumor. The results of this study indicate that mitotane is effective and relatively safe for the treatment of dogs with PDH. Of the dogs treated for longer than 3 months, over 80% were considered to have a good to excellent response to treatment. Adverse effects, although they did occur with some frequency, were generally not lifethreatening, were related to the development of low serum cortisol concentrations, and usually resolved PITUITARY-DEPENDENT hyperadrenocorticism (PDH), a syndrome characterized by excessive corticosteroid production secondary to oversecretion of ACTH by the pituitary gland with resultant bilateral adrenocortical

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Section: Discussionmentioning

confidence: 98%

Mitotane (o, p‘‐DDD) Treatment of 200 Dogs with Pituitary‐Dependent Hyperadrenocorticism

Kintzer

Peterson

1991

Veterinary Internal Medicne

117

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“…Low bioavailability of o,pЈDDD treatment is a well-known drawback of this drug. Both the low absorption rate of o,pЈDDD and its lipophilic nature partly explain this characteristic (36).…”

Section: Discussionmentioning

confidence: 99%

Plasma Concentrations of o,p′DDD, o,p′DDA, and o,p′DDE as Predictors of Tumor Response to Mitotane in Adrenocortical Carcinoma: Results of a Retrospective ENS@T Multicenter Study

Hermsen

Fassnacht

Terzolo

et al. 2011

The Journal of Clinical Endocrinology & Metabolism

158

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“…1 In the dog, the treatment most commonly used involves the administration of the adrenocorticolytic agent mitotane (o,p'-DDD) (Lysodren, Bristol-Myers Squibb) to suppress adrenal function until the gland no longer responds to exogenous ACTH. 2 Failure of this treatment is usually ascribed to misdiagnosis of adrenal tumours, misdiagnosis of hyperadrenocorticism, improper administration of the drug (for example dosing on an empty stomach), 3 use of inactive drug, or concomitant administration of anticonvulsants or other drugs that may mimic the signs of hyperadrenocorticism. 4 An occasional dog requires either a longer than normal course of treatment or a larger than usual dose.…”

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confidence: 99%

Mitotane (o, DDD) resistance in a dog with pituitary‐dependent hyperadrenocorticism and phaeochromocytoma

Bennett

Espinosa

1998

Aust Veterinary J

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A dog was presented with a 2 year history of polyuria and polydipsia due to pituitary-dependent hyperadrenocorticism. A low-dose dexamethasone suppression test and measurement of plasma ACTH concentration confirmed the diagnosis. Treatment was instituted with mitotane at 44 mg/kg/day and then 88 mg/kg/d without complete resolution of signs. The dog collapsed with signs consistent with liver disease and was euthanased. Necropsy revealed a phaeochromocytoma of the left adrenal medulla with extensive metastases to the liver. A chromophobe adenoma of the pars intermedia of the pituitary was found.

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Systemic availability of o,p’-ddd in normal dogs, fasted and fed, and in dogs with hyperadrenocorticism

Cited by 31 publications

References 15 publications

Mitotane (o, p‘‐DDD) Treatment of 200 Dogs with Pituitary‐Dependent Hyperadrenocorticism

Mitotane (o, p‘‐DDD) Treatment of 200 Dogs with Pituitary‐Dependent Hyperadrenocorticism

Plasma Concentrations of o,p′DDD, o,p′DDA, and o,p′DDE as Predictors of Tumor Response to Mitotane in Adrenocortical Carcinoma: Results of a Retrospective ENS@T Multicenter Study

Mitotane (o, DDD) resistance in a dog with pituitary‐dependent hyperadrenocorticism and phaeochromocytoma

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