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Pharmacodynamic and pharmacokinetic modelling of amlodipine in feline

hypertensive patients

Conference Paper · September 2014

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3 authors, including:

Ludovic Pelligand Mirja K Huhtinen

Royal Veterinary College Orion Corporation
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 PHARMACODYNAMIC AND PHARMACOKINETIC MODELLING OF AMLODIPINE
IN FELINE HYPERTENSIVE PATIENTS L Pelligand1, M Huhtinen2, J Elliott1 1Royal
Veterinary College, London UK; 2Orion Corp..

Amlodipine is the treatment of choice for feline hypertension. Limited published data exist
on serum drug concentrations achieved in hypertensive cats. The aim of the study was to
assess serum amlodipine concentrations in cats treated with a new formulation of amlodipine
and to relate these to the blood pressure reduction achieved.

Seventy-seven client-owned hypertensive cats were enrolled into a randomized, double-

blind and placebo controlled study consisting of two phases. In phase one, 42 cats (Group A)
received 0.125 mg/kg amlodipine once daily for 14 days. If they were deemed to have
responded (see below) the dose remained the same to day 28. For non-responders, the dose
was increased to 0.25 mg/kg. Thirty-five cats (Group B) received placebo following the same
protocol. Blood pressure was measured using high definition oscillometry. A responder was
defined as a cat showing a decrease of systolic blood pressure (SBP) to ≤150 mmHg or a
decrease from baseline of ≥15%. Following day 28 (phase 2), Group A continued on
amlodipine and Group B switched to amlodipine and the dose adjusted as per phase 1. Both
groups were followed for 90 days on amlodipine. Blood was collected at days 28 (Group A)
and 90 (both Groups) and serum [amlodipine] measured by liquid chromatography mass
spectrometry. The SBP measured on treatment was calculated as percentage of the baseline
SBP and plotted against serum [amlodipine] using a sigmoidal Emax model (WinNonLin
software). Data are expressed as mean ± SE.

The serum concentrations of Group A cats that remained on 0.125 mg/kg were 29.8 ± 2.5
ng/ml whereas those switched to 0.25 mg/kg were 51.2 ± 7.8 ng/ml. When data from groups A
and B were pooled, a sigmoidal relationship between percentage baseline SBP and serum
[amlodipine] was found. Estimated values of lowest percentage baseline blood pressure on
treatment (Emax) was 83.1 ± 1.7%, with an EC50 value of 10.4 ± 2.6 ng/ml and a slope
function of 2.5 ± 1.2. The serum concentration required to reduce blood pressure by 15% was
estimated to be 20 ng/ml.

The present study related blood pressure reduction to serum [amlodipine] in naturally
occurring feline hypertension. The limitations of this study were the limited number of blood
samples collected and the lack of information relating to the exact timing of blood sampling
relative to dosing in some cats. However, these data could be used to define appropriate
therapeutic serum [amlodipine] in hypertensive cats.

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