The effect of concurrent clopidogrel and omeprazole administration on clopidogrel metabolism and platelet function in healthy cats

Abstract

Background: Some studies in humans show that the concurrent use of clopidogrel and omeprazole decreases plasma clopidogrel active metabolite (CAM) concentrations and clopidogrel antiplatelet effects. Whether this drug interaction occurs in cats is unknown.

Hypothesis: We hypothesized that administration of clopidogrel with omeprazole would decrease plasma CAM concentrations and decrease clopidogrel antiplatelet effects in healthy cats.

Animals: Ten domestic cats.

Methods: In this 2-sequence, 2-period, 2-treatment randomized crossover study, healthy cats were randomly assigned to receive clopidogrel only (18.75 mg PO q24h) or clopidogrel with omeprazole (1 mg/kg PO q12h) for 10 days, followed by a 2-week washout period, and then the opposite treatment for another 10 days. Blood was collected by jugular venipuncture on days 0, 5, and 10. Plasma CAM concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry. Platelet function was evaluated using Plateletworks, Multiplate Analyzer, and Platelet Function Analyzer-100 (PFA-100).

Results: Multiplate Analyzer and PFA-100 detected no difference in platelet function between days or treatment groups. Plateletworks detected a significant difference (P < .001) in platelet function from day 0 to 5 and day 0 to 10 in both treatment groups but no difference between treatment groups. Plasma CAM concentrations were significantly lower on day 10 (P < .02) in cats receiving both medications versus clopidogrel only.

Conclusions and clinical importance: Concurrent omeprazole and clopidogrel administration was associated with altered pharmacokinetics on day 10, but no difference in pharmacodynamics between the 2 treatment groups. The short-term use of clopidogrel and omeprazole does not seem to alter platelet function significantly.

Keywords: Multiplate Analyzer; Platelet Function Analyzer‐100; Plateletworks; clopidogrel active metabolite.

FIGURE 1

Platelet Function Analyzer‐100 (PFA‐100) closure times in seconds in cats treated with clopidogrel only (C only) or concurrent clopidogrel with omeprazole (C + O). The box and whisker plots demonstrate the median (line), interquartile range (box), and total range (whiskers). Outliers are represented by points outside of the whiskers.

FIGURE 2

Multiplate analyzer using adenosine diphosphate agonist results showing area under the curve in cats treated with clopidogrel only (C only) or concurrent clopidogrel with omeprazole (C + O). The box and whisker plots demonstrate the median (line), interquartile range (box), and total range (whiskers). Outliers are represented by points outside of the whiskers.

FIGURE 3

Percent aggregation determined by Plateletworks in cats treated with clopidogrel only (C only) or concurrent clopidogrel and omeprazole (C + O). The box and whiskers plot demonstrate the median (line), interquartile range (box), and total range (whiskers). Outliers are represented by points outside the whiskers. * and ** are statistically different from concentrations on day 0 for C and C + O, respectively (P < 0.05).

FIGURE 4

Clopidogrel active metabolite derivatized (CAM‐D) plasma concentrations measured in 10 cats on day 5 and day 10 after starting daily treatment with clopidogrel only (C only) or with concurrent clopidogrel with omeprazole (C + O). Each cat received both treatments in a randomized cross‐over design with at least 2 weeks of washout between treatments. Filled circles represent CAM‐D concentrations for individual cats with connecting lines indicating the differences between treatments. Significantly lower CAM‐D concentrations were observed with C + O treatment compared with C‐only treatment on day 10 (P = 0.02; paired t test) but not on day 5 (P > 0.05).