Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

STEROIDS
Clinical applications
Mibolerone is labeled in the USA for estrus prevention
in bitches. Testosterone derivatives have been promoted
as stimulants of libido, spermatogenesis and infertility,
with no data supporting these claims.
Formulations and dose rates
For estrus postponement, beginning at least 30 d prior to preestrus
in the bitch but not prior to the first estrus
• The dose of mibolerone is weight and breed dependent (0.5–
12 kg, 30 µg/d; 12–23 kg, 60 µg/d; 23–45 kg, 120 µg/d;
>45 kg, 180 µg/d; and German shepherd type-bitch, 180 µg/d
PO)
• Treatment can continue for a maximum of 2 years. However,
the drug is not recommended in bitches that will be mated.
• It has been proposed that mibolerone may be used for the
same purpose in cats but this use is not recommended because
of the narrow therapeutic index.
Pharmacokinetics
Mibolerone is well absorbed from the gastrointestinal
tract, metabolized in the liver and excreted in the urine
and feces.
Adverse effects
Mibolerone may induce:
● premature epiphyseal closure
● clitoral enlargement and vaginitis, especially in
immature bitches
● abnormal behavior
● urinary incontinence
● riding behavior
● epiphora
● hepatic changes
● increased renal weight in adults.
Adverse effects usually resolve after discontinuation of
therapy, with the exception of clitoral hypertrophy.
Contraindications and precautions
Mibolerone is contraindicated in:
● dogs with androgen-dependent conditions
● pregnancy (it causes masculinization of female
fetuses)
● lactating bitches
● Bedlington terriers
● dogs with hepatic or renal disease.
Fatalities have been reported in cats treated with doses
as low as 120 µg/d.
Known drug interactions
Mibolerone should not be used concurrently with progestins
or estrogens.
Antiandrogenic drugs
EXAMPLES AND
MECHANISMS OF ACTION
Flutamide is a nonsteroid pure antiandrogen drug that
directly blocks androgenic receptors. It has no adverse
effect on the hypothalamus-pituitary function. It has proved
successful in reducing prostatic hyperplasia without
alteration of semen or libido.
Finasteride is a 4-azasteroid synthetic drug that inhibits
5α-reductase, an enzyme responsible for the metabolism of
testosterone to dihydrotestosterone in the prostate, liver
and skin. Dihydrotestosterone is the primary intracellular
hormone responsible for prostate development and
function.
Clinical applications
These drugs are predominantly used for treatment of
prostatic diseases in dogs, including canine benign prostatic
hyperplasia.
Formulations and dose rates
Only fi nasteride will be discussed.
• 1 mg/kg daily PO for 21 weeks. Treated dogs had a marked
decrease in prostate size 5–15 weeks after treatment began.
The prostate size was signifi cantly reduced (30% of the initial
value) and fertility was fully restored after a 20–22 week
recovery period
• Reduced doses of 0.1 mg/kg or 0.5 mg/kg daily PO for
16 weeks have proved to be effective (43% reduction of the
prostatic volume). Finasteride treatment reduced the volume of
the ejaculates without affecting sperm number, sperm defects,
libido or fertility after artifi cial insemination
Pharmacokinetics
Finasteride is absorbed in humans from the gastrointestinal
tract and absorption is unaffected by food. Of
absorbed finasteride, 90% is bound to plasma proteins.
It is metabolized by the liver and excreted in both urine
and feces. The half-life is about 6 h. A single dose of
finasteride in humans causes reduced dihydrotestosterone
for about 24 h.
Adverse effects
● In humans, adverse effects reported are mild, including
decreased libido, reduced volume of ejaculate
and impotence.
● In dogs treated at 1 mg/kg/d PO for 21 weeks, no
long-term effects of the drug were noted. After 5–15
weeks of treatment, sperm concentration increased
and prostatic fluid volume decreased to the point
that ejaculates were no longer collectable, in spite of
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