Introduction: Prolactinoma is the most commonly occurring hormonally active pituitary tumor. In most cases, dopamine receptor agonists (DA) as a monotherapy are effective. However, approximately 10% of patients with prolactinomas fail to achieve normalization of serum prolactin levels during treatment with DA, which indicates resistance to this group of drugs.
Aims: The goal was to study the pharmacokinetics of cabergoline in patients harboring prolactinomas sensitive and resistant to cabergoline.
Materials and methods: We evaluated the levels of cabergoline in blood plasma by tandem mass spectrometry. A single determination of the level of cabergoline in plasma during long-term treatment was performed in 18 patients with prolactinomas, of which six were sensitive to dopamine agonist therapy, 12 were resistant. 10 patients (2 -sensitive and 8 resistant) underwent also measurement of cabergoline levels during the pharmacokinetic test (0, 30, 60, 120, 240 min after patient took 1 tablet of cabergoline (0.5 mg) orally). The test was performed 7 days after the last dose of cabergoline. To determine cabergoline in blood plasma, at 9:00 am a blood sample was taken (0 minute), then blood was taken 30, 120 and 240 minutes after taking the drug.
Results: The concentration of cabergoline in the blood plasma at the 0 minute of the test was not different in patients sensitive and resistant to DA (Mann Whitney U-test P=0.147). In the group of sensitive patients a correlation was found between the level of cabergoline at 0 minute and the dose of cabergoline that the patient constantly takes for a long time (r=0.89, P=0.019). Among resistant patients this correlation was not found (r=0.39, P=0.238). The pharmacokinetic test in sensitive patients did not reveal any significant changes in the level of cabergoline during the test (P=0.392). In resistant patients there were significant differences in the level of cabergoline (P=0.0119). A comparative analysis of the data showed that the concentration of cabergoline in the blood of patients who are resistant to treatment with DA increases sharply by 120 minutes of the sample. A statistically significant difference was found comparing levels at 0 and 120 minutes by the Wilcoxon criterion, P=0.012.
Conclusion: Thus, the pharmacokinetics of cabergoline differ in patients sensitive and resistant to treatment with DA, thereby may contribute to the low effectiveness of treatment in patients with prolactinomas resistant to treatment with DA, and predetermine the lack of effect of dose escalation of the drug.
18 - 21 May 2019
European Society of Endocrinology