RU-2861630-C1 - METHOD FOR INDIVIDUALISED SELECTION OF DOSES OF MEDICINAL PRODUCTS FOR TREATMENT OF PATIENTS WITH CHRONIC HYPOPARATHYROIDISM

RU2861630C1RU 2861630 C1RU2861630 C1RU 2861630C1RU-2861630-C1

Abstract

FIELD: medicine; endocrinology. SUBSTANCE: invention can be used for the individualised selection of doses of medicinal products for the treatment of patients with chronic hypoparathyroidism. Determining age, total blood calcium level, blood phosphorus level, current dose of alfacalcidol, ratio of current dose of calcium carbonate/urinary calcium level, current dose of cholecalciferol, frequency of administration of calcium carbonate and alfacalcidol per day, and target calcium level. Processing the obtained data using a pre-trained ExtraTreesRegressor machine learning model and obtaining data on the adjusted dose of alfacalcidol, and/or calcium carbonate, and/or cholecalciferol and the frequency of administration per day of alfacalcidol and/or calcium carbonate to decide on a treatment regimen. EFFECT: reducing the risk of developing side effects when selecting drug doses and reducing the time to achieve the target serum calcium level by assessing the totality of the most significant indicators, increasing the accuracy of selecting drug therapy doses. 2 cl, 7 tbl, 6 ex

Inventors

MOKRYShEVA Natalia Georgievna
Eremkina Anna Konstantinovna
Kovaleva Elena Vladimirovna
ELFIMOVA Alina Rinatovna
Pershina-Miliutina Anastasiia Pavlovna

Dates

Publication Date: 20260506
Application Date: 20250609

Claims (2)

1. A method for individualized selection of drug doses for the treatment of patients with chronic hypoparathyroidism, characterized by determining age, total blood calcium level, blood phosphorus level, current dose of alfacalcidol, current calcium carbonate/daily urine calcium ratio, current dose of cholecalciferol, frequency of daily intake of calcium carbonate and alfacalcidol preparations, and target blood calcium level, then processing the obtained data using a pre-trained ExtraTreesRegressor machine learning model, which is an ensemble of decision trees consisting of 12 decision trees with a depth of 9, resulting in data on the adjusted dose of alfacalcidol and/or calcium carbonate and/or cholecalciferol preparations and the frequency of daily intake of alfacalcidol and/or calcium carbonate preparations for making a decision on a treatment regimen.
2. The method according to claim 1, characterized in that the target level of total calcium in the blood is from 2.1 to 2.3 mmol/l.

Description

The invention relates to medicine, specifically endocrinology, specifically the development of clinical decision support systems. Predicting dose adjustments for medications such as alfacalcidol, calcium carbonate, and cholecalciferol to achieve target total calcium levels in patients with chronic hypoparathyroidism is an important clinical task. Chronic hypoparathyroidism is characterized by a decrease in the level of parathyroid hormone (PTH), which leads to a disruption in calcium and phosphorus metabolism in the body. Regularly measuring calcium and phosphorus metabolism parameters, primarily total serum calcium levels (the reference level is usually 2.1-2.5 mmol/L), allows physicians to accurately adjust the doses of medications such as alfacalcidol and calcium carbonate. This is especially important, as calcium levels can vary due to various factors. Correction of total calcium levels for albumin levels is necessary to exclude false-negative or false-positive calcemia results due to changes in plasma protein concentrations. Regular monitoring of parameters helps prevent conditions such as hypocalcemia (low blood calcium levels) and hypercalcemia (high blood calcium levels), which are associated with serious complications, including cardiac arrhythmias and the development of functional (decreased glomerular filtration rate) and structural (nephrolithiasis, nephrocalcinosis) kidney disorders. Maintaining serum phosphorus levels within the reference range (usually 0.74-1.52 mmol/L) and daily urinary calcium levels within the target range (according to clinical guidelines for hypoparathyroidism, no more than 6.25 mmol/day for women and no more than 7.5 mmol/day for men) is essential for successful treatment of hypoparathyroidism and the prevention of complications. Exceeding these values indicates a lack of laboratory compensation for the disease and the need to adjust the doses of alfacalcidol and calcium supplements. High calcium in daily urine can lead to renal complications - urolithiasis and decreased renal function, and hyperphosphatemia (increased phosphorus levels) - to extraskeletal calcification (see Kovaleva E.V., Eremkina A.K., Krupinova Yu.A., Mirnaya S.S., Kim I.V., Kuznetsov N.S., Andreeva E.N., Karonova T.L., Kryukova I.V., Mudunov A.M., Sleptsov I.V., Melnichenko G.A., Mokrysheva N.G., Dedov I.I. Review of clinical guidelines for hypoparathyroidism. Problems of Endocrinology. 2021; 67 (4): 68-83 (https://doi.org/10.14341/probl12800). Drug therapy is recommendedAll patients with chronic hypoparathyroidism who have symptoms of hypocalcemia and an albumin-corrected calcium level of less than 2.0 mmol/L are recommended to undergo a treatment trial followed by an assessment of their overall well-being. Hypoparathyroidism is treated with active forms of vitamin D and its analogues (alfacalcidol, calcitriol) in combination with calcium supplements. Using formulas to calculate the required dosage for chronic hypoparathyroidism helps doctors more accurately adjust therapy based on the patient's individual indicators. Furthermore, patients with hypoparathyroidism, as well as the general population, often experience concomitant vitamin D deficiency or insufficiency. Therefore, supplementation with native forms of vitamin D (cholecalciferol) is advisable for its correction. For the Russian population, optimal 25(OH) vitamin D levels are set at 30-60 ng/ml (75-150 nmol/l). 25(OH) vitamin D levels above 100 ng/ml (250 nmol/l) may cause vitamin D toxicity and are not recommended. Treatment with alfacalcidol and calcitriol does not significantly affect serum 25(OH) vitamin D levels. According to federal clinical guidelines, the target level of total or albumin-corrected blood calcium for the treatment of hypoparathyroidism should be maintained within a narrow range of 2.1-2.3 mmol/L. These values serve as a guideline for most physicians and are used to determine hypoparathyroidism treatment goals and assess the degree of disease compensation. Deviations from these target parameters are permitted in individual cases based on the clinical course of the disease. Before initiating treatment, it is important to establish baseline serum total calcium and phosphorus levels to determine the initial dosage. After starting treatment, laboratory parameters (blood calcium and phosphorus, as well as 24-hour urine calcium) and the patient's condition should be regularly assessed. For example, if blood calcium levels do not reach target values, dosage increases may be necessary, and if they exceed the target values, dosage reduction may be necessary. Dosing of medications for the treatment of hypoparathyroidism is largely empirical and depends on the physician's experience. The decision to adjust the dosage is based on laboratory parameters of phosphorus and calcium metabolism, data on previous treatment, and the patient's condition. It is important to note that physicians' experience in managing patients with chronic