Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 23 DRUGS AND REPRODUCTION
Formulations and dose rates—cont’d
overall success rate in treating pyometra in bitches: 84.4% vs
60%
• Combination of aglepristone and PGE 1 : the concomitant use of
aglepristone 10 mg/kg at day 1 (d1), d2, d8, d15 (with a fi nal
treatment on d29 if some vulvar discharge still persists) and
misoprostol (10 µg/kg PO q.12 h d3 to d12) leads to a
signifi cant clinical improvement in 75% of cases without the
side effects of PGF 2α
• Use of aglepristone alone: aglepristone 10 mg/kg has been
used to treat open or closed pyometra at day 1 (d1), d2, d8 and
d15 (with a fi nal treatment on d29 if some vulvar discharge still
persists). In cases of closed-cervix pyometra, a purulent vulvar
discharge was observed from 36 to 48 h after the start of
treatment, due to the induced opening of the uterine cervix. The
pyometra resolved in most cases.
Induction of parturition
It may be desirable to induce parturition during daylight or working
hours, thus facilitating its supervision by the bitch’s owners. Although
some success using aglepristone for this purpose has been reported,
the studies have only been performed in beagle bitches. Therefore, it
is too early to confi rm the effi cacy of the following experimental
procedures.
• Use of aglepristone plus oxytocin or PGF 2α: aglepristone (15 mg/
kg SC) was administered at 58 d of pregnancy in 10 bitches;
24 h later, the bitches were treated SC with either oxytocin
(0.15 UI/kg) or the synthetic prostaglandin alfaprostol (0.08 mg/
kg) every 2 h until parturition. On average, parturition
commenced 32 h (29.7–34.5 h) after aglepristone administration.
In a further study using aglepristone and oxytocin with the
same protocol, the onset of induced parturition in beagle
bitches occurred between 29.7 and 32 h
• Use of aglepristone alone: aglepristone (15 mg/kg) was
administered twice (q.9 h) at 58 d of pregnancy. Expulsion of
the fi rst pup occurred between 35 and 56 h after treatment
(mean 41.0 ± 3.7 h)
Planning of an elective cesarean section
• Injection of 15 mg/kg aglepristone 18–24 h before a planned C-
section may induce fi nal fetal maturation, thus preventing the
release of premature puppies. However, further studies are
needed to confi rm this hypothesis
Treatment of acromegaly (growth hormone excess)
• Acromegaly in dogs (but not cats) is almost always due to a
progestin-induced hypersecretion of growth hormone (GH). In a
recent study, preliminary data suggested that aglepristone may
be effective in treating acromegaly in bitches
IN QUEENS
Induced abortion
• The dose is slightly higher than in dogs: two repeated SC
injections 15 mg/kg at 24-h intervals between day 0 and day
45 after mating. The effectiveness of this protocol is greater
before implantation (95%) than after implantation (85%).
Termination of pregnancy is achieved in 50% of the queens
within 3 d. In most cases, the following interestrus interval is
signifi cantly shortened and the queen rapidly comes into heat
with high fertility.
Conservative treatment of pyometra
• The combination of aglepristone and PGF 2α described above
may be successfully used in queens.
Treatment of mammary fibroadenomatosis
Different protocols have been published.
• 20 mg/kg (SC once a week) until complete mammary
regression
• 10 mg/kg on two consecutive days, once weekly
• Usually a minimum of 4–6 weeks is needed for a complete
mammary regression
Pharmacokinetics
There are no data on aglepristone pharmacokinetics in
dogs and cats in the literature but they are probably
similar to mifepristone. Enteric absorption of mifepristone
after oral administration occurs very quickly. The
transport of mifepristone in the blood occurs with a
high binding affinity (98%) to plasma protein. Its
plasma half-life is around 18 h. Its metabolism occurs
mainly in the liver. Elimination occurs mainly in the
feces, via the bile (90%), but also in urine (10%).
Adverse effects
Side effects that may be observed with aglepristone
treatment include restlessness, anorexia, emesis, diarrhea,
drop of rectal temperature, vulvar discharge.
Metritis requiring specific therapy using PGF 2α
developed in 5.7% (5/88) bitches treated for induced
abortion.
Contraindications and precautions
None reported.
Known drugs interaction
None reported.
Testosterone and derivatives
Widely used in the past for a variety of conditions, testosterone
is of no clinical use in small animal reproduction.
The 19-nor-steroid mibolerone is the only related
drug of use.
EXAMPLES
Testosterone cypionate, testosterone propionate and
testosterone ethanate are synthetic esters of testosterone.
Mibolerone or dimethyl-nortestosterone is a synthetic,
androgenic, anabolic steroid.
Mechanism of action
Mibolerone blocks the release of LH from the anterior
pituitary by negative feedback.
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