TY - JOUR
T1 - Pharmacokinetics and pharmacodynamics of pergolide mesylate after oral administration in horses with pituitary pars intermedia dysfunction
AU - Rendle, D. I.
AU - Doran, G.
AU - Ireland, Jo
AU - Edwards, S.
PY - 2019/7
Y1 - 2019/7
N2 - Published information on the pharmacokinetic and pharmacodynamic properties of pergolide
is limited. The aim of this study was to investigate the
pharmacokinetic and pharmacodynamic properties of oral pergolide in
horses with pituitary pars intermedia
dysfunction (PPID). The study design was a nonrandomized clinical
trial. Six horses with PPID diagnosed by thyrotropin-releasing hormone
(TRH) stimulation tests received pergolide at 4 μg/kg for 18 d. Plasma
samples for determination of pergolide and ACTH concentration were
collected 0.5 h before and 2 and 12 h after each administration of
pergolide. Maximum plasma concentrations
after the first oral dose of pergolide (0.104–0.684 ng/mL; median
0.261 ng/mL; interquartile range [IQR] 0.184–0.416 ng/mL) were not
significantly different to the maximum steady-state concentration at day
18 (0.197–0.628 ng/mL; median 0.274; IQR 0.232–0.458 ng/mL). Chronic administration
was not associated with drug accumulation (R = 1.09) and pergolide
concentration reached steady state within 3 d. Throughout,
concentrations of pergolide fluctuated considerably, with median plasma
peak concentrations more than four times higher than median trough concentrations. Plasma ACTH
concentration reduced significantly within 12 h of administration with
further reductions occurring up to 10 d after the initiation of
treatment. Although there were parallel fluctuations in the
concentrations of pergolide and ACTH, timing of ACTH measurement in
relation to the administration of pergolide did not have a significant
effect. Alterations in the response to TRH were identified at 8 d with
no further change being identified at 18 d. A small number of horses
were studied. Oral pergolide results in significant suppression of pars
intermedia activity within hours. Pergolide and ACTH concentrations
fluctuated in tandem although correlation was poor. Fluctuations in
pergolide concentration were consistent with a terminal elimination
half-life of less than 12 h. To reduce the level of fluctuation of ACTH,
twice-daily dosing of pergolide may be more appropriate.
AB - Published information on the pharmacokinetic and pharmacodynamic properties of pergolide
is limited. The aim of this study was to investigate the
pharmacokinetic and pharmacodynamic properties of oral pergolide in
horses with pituitary pars intermedia
dysfunction (PPID). The study design was a nonrandomized clinical
trial. Six horses with PPID diagnosed by thyrotropin-releasing hormone
(TRH) stimulation tests received pergolide at 4 μg/kg for 18 d. Plasma
samples for determination of pergolide and ACTH concentration were
collected 0.5 h before and 2 and 12 h after each administration of
pergolide. Maximum plasma concentrations
after the first oral dose of pergolide (0.104–0.684 ng/mL; median
0.261 ng/mL; interquartile range [IQR] 0.184–0.416 ng/mL) were not
significantly different to the maximum steady-state concentration at day
18 (0.197–0.628 ng/mL; median 0.274; IQR 0.232–0.458 ng/mL). Chronic administration
was not associated with drug accumulation (R = 1.09) and pergolide
concentration reached steady state within 3 d. Throughout,
concentrations of pergolide fluctuated considerably, with median plasma
peak concentrations more than four times higher than median trough concentrations. Plasma ACTH
concentration reduced significantly within 12 h of administration with
further reductions occurring up to 10 d after the initiation of
treatment. Although there were parallel fluctuations in the
concentrations of pergolide and ACTH, timing of ACTH measurement in
relation to the administration of pergolide did not have a significant
effect. Alterations in the response to TRH were identified at 8 d with
no further change being identified at 18 d. A small number of horses
were studied. Oral pergolide results in significant suppression of pars
intermedia activity within hours. Pergolide and ACTH concentrations
fluctuated in tandem although correlation was poor. Fluctuations in
pergolide concentration were consistent with a terminal elimination
half-life of less than 12 h. To reduce the level of fluctuation of ACTH,
twice-daily dosing of pergolide may be more appropriate.
KW - Dopamine agonist
KW - Endocrine
KW - Equine Cushing's disease
KW - Laminitis
UR - http://www.scopus.com/inward/record.url?scp=85065422784&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065422784&partnerID=8YFLogxK
U2 - 10.1016/j.domaniend.2019.01.008
DO - 10.1016/j.domaniend.2019.01.008
M3 - Article
C2 - 31082785
AN - SCOPUS:85065422784
VL - 68
SP - 135
EP - 141
JO - Domestic Animal Endocrinology
JF - Domestic Animal Endocrinology
SN - 0739-7240
ER -