Therapeutic Drug Monitoring in Uncontrolled Arterial Hypertension: Result of the Pilot Part of Study

INTRODUCTION: Despite the recently established evidence-based and systemic approach to treatment for arterial hypertension (AH), not in all cases its control can be achieved.

AIM: To conduct a comparative analysis of the concentration of antihypertensive drugs (AHTDs) in blood serum of patients with controlled and uncontrolled AH.

MATERIALS AND METHODS: Fifty six patients were included. Inclusion criteria: age ≥ 18 years, signing of informed consent, established diagnosis of AH, regular intake of any two of study antihypertensive drugs (lisinopril, amlodipine, valsartan) and also of indapamide at stable doses, for women — adequate contraception. According to the results of daily monitoring of the arterial pressure (AP), patients were divided into two groups: the first group — controlled hypertension (AP < 140/90 mmHg; n = 39), the second — uncontrolled hypertension (AP ≥ 140/90 mmHg; n = 17). The mean age of patients in the first group was 65.03 ± 10.80 years, in the second — 63.50 ± 8.31 (p = 0.576). In the first group, women prevailed (64.1% vs. 35.3%, p = 0.047) and the mean body mass index was lower (26.30 ± 1.38 kg/m² vs. 32.20 ± 4.15 kg/m², p = 0.02). In patients of both groups, venous blood was taken in fasting condition in the morning and 2 hours after intake of AHTDs to assess their concentration by high-performance liquid chromatography. The analytical range for lisinopril, indapamide, amlodipine was 5–500 ng/ml, for valsartan — 10–10,000 ng/ml.

RESULTS: In the first group, equilibrium concentration of lisinopril was 2.67 times higher (p = 0.053), and concentration of indapamide in 2 hours after intake was 1.83 times higher (р = 0,084); when normalized to the dose, the differences were leveled out (p > 0.05). Concentrations of amlodipine and valsartan did not differ between the groups both before and 2 hours after intake (p > 0.05). In 3 of 39 (7.7%) patients with controlled hypertension and in one of 17 patients (5.9%, p = 1.0) with uncontrolled hypertension, AHTDs were detected in blood serum, which were not administered to them.

CONCLUSIONS: Results of the pilot part of the study (n = 56) demonstrated the absence of difference between the mean concentrations of the study AHTDs in the blood serum of patients with controlled and uncontrolled AH, and in some cases the presence of traces of AHTDs not administered by the doctor.