A capillary electrophoresis method for the simultaneous determination of the enantiomeric purity and of impurities of the chiral calcimimetic drug cinacalcet hydrochloride has been developed following Quality by Design principles. The scouting phase was aimed to select the separation operative mode and to identify a suitable chiral selector. Among the tested cyclodextrins, (2-carboxyethyl)-β-cyclodextrin and (2-hydroxypropyl)-γ-cyclodextrin (HPγCyD) showed good chiral resolving capabilities. The selected separation system was solvent-modified capillary zone electrophoresis with the addition of HPγCyD and methanol. Voltage, buffer pH, methanol concentration and HPγCyD concentration were investigated as critical method parameters by a multivariate strategy. Critical method attributes were represented by enantioresolution and analysis time. A Box-Behnken Design allowed the contour plots to be drawn and quadratic and interaction effects to be highlighted. The Method Operable Design Region (MODR) was identified by applying Monte-Carlo simulations and corresponded to the multidimensional zone where both the critical method attributes fulfilled the requirements with a desired probability π≥90%. The working conditions, with the MODR limits, corresponded to the following: capillary length, 48.5cm; temperature, 18°C; voltage, 26kV (26-27kV); background electrolyte, 150mM phosphate buffer pH 2.70 (2.60-2.80), 3.1mM (3.0-3.5mM) HPγCyD; 2.00% (0.00-8.40%) v/v methanol. Robustness testing was carried out by a Plackett-Burman matrix and finally a method control strategy was defined. The complete separation of the analytes was obtained in about 10min. The method was validated following the International Council for Harmonisation guidelines and was applied for the analysis of a real sample of cinacalcet hydrochloride tablets.

• Klíčová slova
• Capillary electrophoresis, Chiral separation, Cinacalcet, Impurities, Method operable design region, Quality by Design,
• MeSH
• beta-cyklodextriny chemie   MeSH
• cinakalcet chemie   izolace a purifikace   MeSH
• elektroforéza kapilární metody   MeSH
• gama-cyklodextriny chemie   MeSH
• hodnocení rizik MeSH
• koncentrace vodíkových iontů MeSH
• kontaminace léku MeSH
• metoda Monte Carlo MeSH
• pravděpodobnost MeSH
• rozpouštědla MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny MeSH
• betadex MeSH Prohlížeč
• cinakalcet MeSH
• gama-cyklodextriny MeSH
• gamma-cyclodextrin MeSH Prohlížeč
• rozpouštědla MeSH

OBJECTIVE: Medical management of primary hyperparathyroidism (PHPT) is important in patients for whom surgery is inappropriate. We aimed to describe clinical profiles of adults with PHPT receiving cinacalcet. DESIGN: A descriptive, prospective, observational study in hospital and specialist care centres. METHODS: For patients with PHPT, aged 23-92 years, starting cinacalcet treatment for the first time, information was collected on dosing pattern, biochemistry and adverse drug reactions (ADRs). Initial cinacalcet dosage and subsequent dose changes were at the investigator's discretion. RESULTS: Of 303 evaluable patients with PHPT, 134 (44%) had symptoms at diagnosis (mostly bone pain (58) or renal stones (50)). Mean albumin-corrected serum calcium (ACSC) at baseline was 11.4 mg/dl (2.9 mmol/l). The reasons for prescribing cinacalcet included: surgery deemed inappropriate (35%), patient declined surgery (28%) and surgery failed or contraindicated (22%). Mean cinacalcet dose was 43.9 mg/day (s.d., 15.8) at treatment start and 51.3 mg/day (31.8) at month 12; 219 (72%) patients completed 12 months treatment. The main reason for cinacalcet discontinuation was parathyroidectomy (40; 13%). At 3, 6 and 12 months from the start of treatment, 63, 69 and 71% of patients, respectively, had an ACSC of ≤10.3 mg/dl vs 9.9% at baseline. Reductions from baseline in ACSC of ≥1 mg/dl were seen in 56, 63 and 60% of patients respectively. ADRs were reported in 81 patients (27%), most commonly nausea. A total of 7.6% of patients discontinued cinacalcet due to ADRs. CONCLUSIONS: Reductions in calcium levels of ≥1 mg/dl was observed in 60% of patients 12 months after initiation of cinacalcet, without notable safety concerns.

• MeSH
• cinakalcet MeSH
• dospělí MeSH
• lékařská praxe - způsoby provádění statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• naftaleny terapeutické užití   MeSH
• primární hyperparatyreóza farmakoterapie   epidemiologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Názvy látek
• cinakalcet MeSH
• naftaleny MeSH

Calciphylaxis is a rare complication of chronic renal failure mostly with poor prognosis. Painful lesions on various skin surface areas are the most prominent feature of this serious disease. Subsequent infection of necrotic skin tissue is associated with the risk of sepsis. Pathophysiology is unclear, but several risk factors are known. The most important risk factor is impaired calcium-phosphate metabolism. Our paper describes two cases of different forms of calciphylaxis in patients with chronic renal failure. In the first case, pamidronate and cinacalcet were used for treatment. In the second described case, calciphylaxis was associated with secondary hyperparathyroidism and immediate subtotal parathyroidectomy was performed. Both patients were successfully treated, using systemic approach as well as dedicated local care for healing of skin wounds.

• MeSH
• antiflogistika terapeutické užití   MeSH
• bisfosfonáty terapeutické užití   MeSH
• chronické selhání ledvin komplikace   patologie   terapie   MeSH
• cinakalcet MeSH
• dialýza ledvin škodlivé účinky   MeSH
• kalcifylaxe farmakoterapie   etiologie   patologie   MeSH
• kožní nemoci etiologie   patologie   MeSH
• kůže patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• naftaleny terapeutické užití   MeSH
• pamidronát MeSH
• paratyreoidektomie MeSH
• sekundární hyperparatyreóza etiologie   patologie   chirurgie   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika MeSH
• bisfosfonáty MeSH
• cinakalcet MeSH
• naftaleny MeSH
• pamidronát MeSH

A nonagenarian hypertensive man with chronic kidney disease (CKD) was admitted to the emergency department for gastrointestinal symptoms and worsening symptoms of depression. Severe hypercalcemia (15.3 mg/dL) was found and he was hospitalized. Fluids, loop diuretics and glucocorticoids were administered intravenously, which partially reduced calcium levels over a few days and improved his clinical condition. PTH levels proved increased (306 pg/mL) and 25-OHD levels were reduced; primary hyperparathyroidism (PHPT) was diagnosed. Neck ultrasonography (USG) did not show parathyroid enlargement, nor did 99mTechnetium-sestamibi (SESTAMIBI) scintigraphy reveal hyperfunctioning parathyroid glands. By contrast, 18F-choline PET/CT evidenced a nodule located close to the oesophagus, behind the right thyroid lobe, which proved compatible with a hyperfunctioning parathyroid gland. Since the patient declined surgery, and zoledronate was unfit owing to areas of rarefaction of the jaw, the calcimimetic cinacalcet was started; the dosage was progressively titrated up to 120 mg/day with normalisation of calcium levels over time. PTH levels, however, proved erratic and showed an upward trend over the first year of therapy; however its levels partially decreased following increase of vitamin D levels by replacement therapy. Cinacalcet is a useful and safe drug, which can normalise calcium levels and improve the clinical condition, even in very old patients with severe PHPT who decline or are unfit for surgery.

• Klíčová slova
• 18F-Choline PET/CT, cinacalcet, hypercalcemia, primary hyperparathyroidism,
• MeSH
• cholin MeSH
• cinakalcet terapeutické užití   MeSH
• hyperkalcemie etiologie   MeSH
• kalcimimetika terapeutické užití   MeSH
• lidé MeSH
• PET/CT metody   MeSH
• primární hyperparatyreóza komplikace   diagnostické zobrazování   farmakoterapie   MeSH
• radiofarmaka MeSH
• radioizotopy fluoru MeSH
• senioři nad 80 let MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• cholin MeSH
• cinakalcet MeSH
• Fluorine-18 MeSH Prohlížeč
• kalcimimetika MeSH
• radiofarmaka MeSH
• radioizotopy fluoru MeSH

A rapid HPLC method for the analytical resolution of cinacalcet enantiomers was developed. Four chiral columns (two amylose and two cellulose type) were evaluated in RP systems. Excellent enantioseparation with a resolution of more than 6 was achieved on Chiralpak AY (amylose 5-chloro-2-methylphenylcarbamate chiral stationary phase) using 10 mM triethylamine (pH 8.0)-acetonitrile (40 + 60, v/v) mobile phase. Validation of the HPLC method, including linearity, LOD, LOQ, precision, accuracy, and selectivity, was performed according to the International Conference on Harmonization guidelines. The method was successfully applied for the determination of (S)-cinacalcet in enantiopure active pharmaceutical ingredient (R)-cinacalcet.

• MeSH
• algoritmy MeSH
• alkoholy MeSH
• cinakalcet MeSH
• indikátory a reagencie MeSH
• koncentrace vodíkových iontů MeSH
• limita detekce MeSH
• naftaleny chemie   MeSH
• polysacharidy chemie   MeSH
• pufry MeSH
• referenční standardy MeSH
• reprodukovatelnost výsledků MeSH
• rozpouštědla MeSH
• stereoizomerie MeSH
• teplota MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkoholy MeSH
• cinakalcet MeSH
• indikátory a reagencie MeSH
• naftaleny MeSH
• polysacharidy MeSH
• pufry MeSH
• rozpouštědla MeSH

BACKGROUND: The cost and effectiveness patterns in the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients in the Czech Republic are unknown. METHODS: 52 dialysis patients from 17 centers were followed up in a multicenter prospective study of laboratory and clinical (hospitalization rate, clinical complaints questionnaire) responses to 12-month cinacalcet treatment. Treatment patterns and cost (including phosphate binders, vitamin D, and cinacalcet) were evaluated. RESULTS: The mean s-Ca dropped significantly from 2.36 ± 0.24 to 2.21 ± 0.20 mmol/l, s-P from 2.45 ± 0.54 to 2.01 ± 0.53 mmol/l, Ca×P from 5.79 ± 1.25 to 4.42 ± 1.13 mmol²/l², and iPTH dropped from 919.0 ± 465.6 to 372.1 ± 294.6 pg/ml. The mean cinacalcet dose reached 44.1 ± 23.0 mg/day after 12 months. Itching intensity decreased significantly. No change in hospitalization rate was observed. The direct cost of daily SHPT treatment rose significantly from EUR 8.77 ± 9.59 to 20.62 ± 9.22. CONCLUSIONS: Cinacalcet decreased elevated s-Ca, s-P, Ca×P, and iPTH, alleviated itching, and significantly raised the SHPT treatment cost. A minority of patients reached K/DOQI targets, especially due to poor phosphate control caused by insufficient phosphate binder treatment, cinacalcet underdosing, and advanced SHPT.

• MeSH
• cinakalcet MeSH
• dialýza ledvin MeSH
• dospělí MeSH
• fosfáty krev   MeSH
• hodnocení léčiv MeSH
• lidé středního věku MeSH
• lidé MeSH
• naftaleny ekonomika   terapeutické užití   MeSH
• náklady na zdravotní péči MeSH
• následné studie MeSH
• parathormon krev   MeSH
• prospektivní studie MeSH
• průzkumy a dotazníky MeSH
• sekundární hyperparatyreóza farmakoterapie   ekonomika   MeSH
• senioři MeSH
• vápník krev   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• cinakalcet MeSH
• fosfáty MeSH
• naftaleny MeSH
• parathormon MeSH
• vápník MeSH