Описание
Препарат Золинза — это современное противоопухолевое средство, которое используется при прогрессирующей или стойкой первичной кожной Т-клеточной лимфомы, а также при рецидиве после предыдущих системных курсов противоопухолевого лечения. Основное действующее вещество препарата — вориностат.
Эффективность препарата Золинза исследовалась у больных с кожной формы Т-клеточной лимфомы во IIB стадии и выше. Объективный эффект зарегистрирован у 30% пациентов, всего на терапию данным препаратом ответило 46% пациентов. Некоторые визуальные улучшения отмечались у 77 процентов пациентов. У пациентов, страдающих от нестерпимого зуда, также отмечалась положительная динамика.
Показания препарата Золинза
- лечение кожной Т-клеточной лимфомы, несмотря на проведенную системную терапию, которая прогрессирует, рецидивирует или персистирует.
Состав Золинза
- Активное вещество: вориностат 100,0 мг
- Вспомогательные вещества: целлюлоза микрокристаллическая, кроскармеллоза натрия, магния стеарат.
- Оболочка капсулы: титана диоксид (Е171), желатин.
- Чернила: Опакод черный (Opacode Black) S-l-17822: шеллака глазури раствор в этаноле, краситель железа оксид черный, бутанол, изопропанол, пропиленгликоль, аммония гидроксид. Или Опакод черный (Opacode Black) S-1-17823: шеллака глазури раствор в этаноле, краситель железа оксид черный, бутанол, изопропанол, пропиленгликоль, аммония гидроксид.
Фармакологическое действие
Вещество вориностат — сильный ингибитор гистон-деацетилаз (HDAC) — HDAC1, HDAC2 и HDAC3, а также HDAC6. Эти ферменты катализируют отщепление от лизиновых остатков белков ацетиловой группы, в т.ч. белков-факторов транскрипции и гистонов. Противоопухолевое свойство вориностата связано с ингибированием активности HDAC с дальнейшим накоплением ацетилированных белков, включая гистоны. Ацетилирование гистонов сопровождается транскрипционной активацией генов, в т.ч. генов-супрессоров опухолей, а их экспрессия, в свою очередь, индуцирует апоптоз клеток или дифференцировку и подавление опухолевого роста клеток. Концентрация вориностата, вызывающая накопление ацетилированных гистонов, также обусловливает ингибирование клеточного цикла, апоптоз или дифференцировку видоизмененных клеток.
Вориностат по данным исследований на клеточных культурах индуцирует апоптоз у большого числа видоизмененных (опухолевых) клеток. Вориностат на культурах опухолевых клеток при совместном использовании с другими видами противоопухолевой терапии показал дополнительную или синергичную активность, включая лучевую терапию и химиотерапию цитотоксическими препаратами, индукторами дифференцировки клеток, ингибиторами киназ. Вориностат in vivo, на широком диапазоне моделей рака у грызунов, включая модели ксенотрансплантатов злокачественных опухолей молочной железы, толстой кишки, простаты человека показал противоопухолевую активность.
Фармакокинетика
Всасывание
При однократном приеме внутрь вориностата в дозировке 400 мг одновременно с жирной пищей у больных с рефрактерными или рецидивирующими распространенными опухолями средние значения ± стандартное отклонение AUC, Cmax и медианы (диапазона) Tmax составили 5.5±1.8 мкмоль/л×ч, 1.2±0.62 мкмоль/л и 4 (2-10) ч соответственно. При однократном приеме внутрь препарата Золинза в дозиовке 400 мг натощак средние значения AUC, Cmax и медианы Тmах составили 4.2±1.9 мкмоль/л×ч, 1.2±0.35 мкмоль/л и 1.5 (0.5-10) ч соответственно. Одновременный прием вориностата, таким образом, с жирной пищей сопровождается повышением (на 33процента) всасывания и незначительным снижением скорости всасывания (задержка наступления Тmах на 2.5 часа) в сравнении с приемом препарата Золинза натощак. Предполагается, что отклонения фармакокинетических параметров незначительны и не имеют клинического значения.
После многократного приема внутрь вориностата в дозировке 400 мг одновременно с пищей значения Cmax, медианы Тmах, AUC в равновесном состоянии составили 6.0±2.0 мкмоль/л×ч, 1.2±0.53 мкмоль/л и 4 (0.5-14) ч соответственно.
Распределение Золинза
Связывание вориностата с белками плазмы в диапазоне плазменных концентраций от 0.5 до 50 мкг/мл составляет примерно 71процент. Препарат Золинза быстро проникает через плацентарный барьер у кроликов и крыс при введении в суточных дозировках 150 мг/кг и 15 мг/кг соответственно (что соответствует меньшему значению экспозиции, чем у человека по данным AUC0-24). Примерно через 30 мин после введения достигается трансплацентарное равновесие.
Метаболизм
Реакции глюкуронизации и гидролиза с последующим β-окислением являются основными путями метаболизма препарата Золинза. плазменные концентрации двух метаболитов — О-глюкуронида вориностата и 4-анилино-4-оксобутановой кислоты были измерены. Оба метаболита фармакологически неактивны. В равновесном состоянии экспозиция О-глюкуронида вориностата и 4-анилино-4-оксобутановой кислоты в сыворотке крови превышает экспозицию вориностата примерно в 4 и 13 раз соответственно, по сравнению с вориностатом.
In vitro проведенные исследования на микросомах печени человека указывают на незначительную биотрансформацию препарата Золинза ферментами системы цитохрома Р450.
Выведение Золинза
Вориностат преимущественно метаболизируется в печени. Почками выводится в неизмененном виде менее 1% введенной дозы. Таким образом, почечная экскреция на выведение препарата из организма практически не влияет. В моче при достижении равновесного состояния обнаруживали два фармакологически неактивных метаболита вориностата — 4-анилино-4-оксобутановую кислоту в количестве 36±8.6% от введенной дозы вориностата и О-глюкуронид вориностата в количестве 16±5.8% от введенной дозы вориностата. количество обнаруживаемых? таким образом, в моче неизмененного вориностата и двух указанных метаболитов составило в среднем 52±13.3% от принятой дозы вориностата. период полувыведения препарата Золинза и О-глюкуронида составил около 2 часов, а период полувыведения 4-анилино-4-оксобутановой кислоты — примерно 11 часов.
Фармакокинетика у особых групп пациентов
Пол, раса и возраст пациентов, по данным анализа ограниченного объема данных, клинически значимого влияния на фармакокинетические параметры вориностата не оказывали.
Дети.
У детей и подростков до 18 лет фармакокинетические параметры вориностата не изучены.
Пациенты с печеночной недостаточностью.
Вориностат противопоказан к использованию у больных с печеночной недостаточностью тяжелой степени. Препарат Золинза необходимо применять с осторожностью у больных с печеночной недостаточностью легкой и средней степени. Эти рекомендации основаны на данных фармакокинетических исследований. Согласно этим исследованим предполагается, что после приема вориностата риск дозозависимой токсичности выше, у пациентов с тяжелой степенью печеночной недостаточности, чем у пациентов без нарушений функции печени, даже при приеме сниженной дозировки препарата Золинза. Суточная переносимая доза вориностата для больных с легкой и средней степенью печеночной недостаточности составляет 300 мг и 200 мг.
Пациентов с тяжелой степенью печеночной недостаточности из исследования вориностата исключили. Есть ограниченное число больных с печеночной недостаточностью средней степени, которых включили в клинические исследования. клинически значимого различия в развитии побочных эффектов, связанных с функцией печени, не обнаружено, у пациентов с печеночными нарушениями в анамнезе по сравнению с пациентами без таковых.
Пациенты с почечной недостаточностью.
У пациентов с почечной недостаточностью не изучены фармакокинетические параметры препарата. почечная экскреция, следует отметить, не влияет на элиминацию вориностата из организма.
Фармацевтические характеристики Золинза
Капсулы твердые желатиновые, размер №3, непрозрачные, белого цвета, с черной надписью «568» и белой надписью на черном фоне «100 mg». Содержимое капсул — порошок от белого до светло-оранжевого цвета.
Упаковка, срок годности, условия хранения Золинза
По 120 капсул во флаконе. Флакон — из полиэтилена высокой плотности, запаянный защитной мембраной и закрытый пластмассовой крышкой с устройством против вскрытия флакона детьми.
Вместе с инструкцией по применению по одному флакону в картонную пачку.
Препарат Золинза следует хранить в недоступном для детей месте при температуре не выше 30°С.
Срок годности — 3 года. Не использовать по истечении срока годности, указанного на упаковке.
Особые указания
Контакта содержимого капсулы с кожей и слизистыми оболочками следует избегать. При контакте тщательно смыть порошок водой.
Наша компания работает как на территории Казахстана, так и осуществляет доставку в страны ближнего зарубежья. Обращайтесь к нам за консультациями по контактным телефонам.
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It should go with out saying, but utilizing strict form is important.
When building muscle, you want to ensure you maintain the strain on the muscle you are attempting to train. Utilizing momentum, chopping the vary of motion, and doing sloppy
reps limit how much muscle you’ll be able to construct.
If your whole higher body strikes throughout a curl, you are doing it wrong.
You can readily obtain this PDF in a single click on to keep this plan useful in your 3-day-a-week coaching sessions.
It’s fine should you full your cut up routine in eight or 9 days somewhat than 7.
Most individuals do completely nice with a 5 day workout «bro split» as a outcome of the workouts are so centered
on one area of your body and there’s plenty of recovery,
so its onerous to overtrain. This should be enough time to let your muscle get well for the subsequent set but not get cold.
If you are doing very heavy weight and big compound movements,
you might need somewhat extra time between units and that’s completely fantastic.
Just make sure you usually are not resting to the point the place your muscle tissue get chilly.
You will know when you are ready for the subsequent set,
your coronary heart price will tell you. But push
your self as sometimes you will lengthen the remainder
time longer than you really need.
Make sure you separate each training session with no less than one relaxation day.
This routine will work each major muscle group each session and
is designed to enhance your strength and build muscle mass.
Sure, a full body weight training program can get you ripped so long as they’re done with proper intensity and frequency.
Fitbod ensures that these workout plans match your abilities, creating
a motivational yet difficult surroundings for you to maintain progressing and want to progress
in lifting weights. This weightlifting app options
an intuitive gym logger to track the progress of your weightlifting
sessions, which is then graphically displayed by way of
charts. This great function motivates customers to optimize features by recognizing patterns to enhance further.
Ladies will see all of the above once they begin following an everyday exercise routine.
In addition, exercise additionally offers many advantages that are especially important for girls.
But its advantages are much more vital than many of us notice.
The first major concern for girls is their concern of getting bulky.
By stripping the load back to 60 pounds, you are able to use strict kind, the place the only movement
is through the elbow joint. Use a heavy weight and give consideration to the
eccentric with a 3 second decrease of the rep. Focus on fully stretching and elongating the
lats during this unfavorable portion of the rep. That Is because you’ll be
making use of slightly identified method known as Satan Sets.
That’s what occurs when you relaxation more than two minutes between units.
This 12-week powerlifting program will information you through the exact work you need
to do main as much as your next competition. All The Time seek the
guidance of with a professional healthcare professional previous to starting any diet or train program or taking any dietary complement.
By using lighter and heavier training days each week they’ll construct upon one another
to further enhance your maximal power. You could have both
heavy and light coaching days for each of your weekly
major lifts. The second con to this set-up is because of the truth that you may be lifting heavy three
times every week — it doesn’t lend so well for a lot of other activity, similar to heavy sports training.
If you are concerned in high-level athletics, it might be higher to choose a barely much less demanding program so you do not turn into overly fatigued.
One of the largest advantages of this set-up is going to be an elevated frequency of training.
Since you will stimulate so many muscle fibers each other day, you will note a really high release of testosterone, promoting an excellent diploma of muscle mass growth.
For anybody looking to pack on some serious
muscle mass, one of many top priorities might be to determine what one of
the best bodybuilding exercise to comply with is.
If you’ll be able to put more weight on all your bigger lifts, you could not have the power to
add weight to the workouts towards the top. This is perfectly fine as
long as you’re pushing it to failure. Though new exercisers should take it sluggish, eventually you can —
and may — add intensity to your exercise to
maintain and enhance your fitness. It can be a perfect program for somebody
doing one other activity on the side, be it cycling, climbing,
MMA or whatever. If your life is crazy hectic busy, you can additionally simplify this kind of exercise routine.
Additionally, although the squat is a incredible exercise, it doesn’t work one of
many four quadriceps muscles very properly.
We’re speaking a couple of muscle in the course of
the entrance of your leg known as the biceps femoris.
It’s additionally referred to as the «kicking muscle» as a outcome of
it’s the most important muscle for extending your knee.
Don’t be discouraged when you feel like a wobbly flamingo at first.
If you possibly can only do two periods, you do Exercise
A on one day and Workout B on one other. The solely thing
to maintain in mind is to squeeze in no less than one rest day between training classes.
Running a 5-day workout routine has many benefits if you do it correctly.
Right Here are some reasons this could be the best program you ever run. I count on you to maintain the
burden you most likely did final week, and I’ve added some
additional units. Remember, in case you have a set of 8 at 1RIR, then you ought to be
lifting heavier for a set of 6.
For of us with a busy schedule, a full body exercise applications are time environment friendly and may cut your training days down to as little as 3 days per week.
Full physique coaching programs are ideal for the newbie
lifter or for anybody involved in other athletic actions.
Nonetheless, once more, don’t feel the want to rush to advance to another program.
This beginner energy training program doesn’t abruptly stop working after a set variety of weeks.
The finest full physique power coaching workout ought to
include a combination of exercises that focus
on the most important muscle teams, along with workout routines that incorporate all seven motion patterns.
This sort of routine should be completed at least 3 times per
week and will give attention to compound actions. You should also keep in mind when you’ll schedule cardio and a rest
day, which usually occurs in between exercises.
Bodybuilding is kind of a sport, the place to be successful, you have to give one hundred pc to coaching, diet and mental approach.
Heading to the gym daily with the same zeal and dedication could be challenging.
Variations of the snatch and clean & jerk are frequently used
to assist practice specific portions of the movement sample.
These can include the snatch from hip, snatch from knee,
power snatch, power clear, clean & jerk from hip, clear & jerk from knee, cleans,
and so on. This program can be used in preparation for a weightlifting competitors.
Working out produces waste products in the muscle cells—the results
of burning glucose and fat to gas muscular contractions.
That waste buildup attracts water inside muscle cells, and as with a balloon, the extra water that the muscle cell can maintain, the larger the pump
you’ll expertise. The pump essentially stretches the muscle cell, making the muscle itself momentarily bigger and initiating biochemical pathways that prompt everlasting growth.
You will begin with the same weight that you used for
the previous three sets. Maintaining your rest time to a minute will ensure that your total intensity
for this exercise ramps up like a staircase effect.
That should be your 10 reps max, so that you simply
cannot do an 11th rep with out your type breaking down.
You can get by with 1-2 minutes of rest on the isolation movements.
The first two weeks of this system are all
about lifting heavy with mass-building compound exercises.
For every little thing but abs and calves, reps fall in the 6-8 range; for those accustomed to doing units of 8-12, this implies
going heavier than regular.
In this beginner weight coaching program, you need to be looking
to improve your weights by 2lb – 5lb every session. Earlier Than the squat, bench press, and
overhead press, use an empty barbell with 2 units of 5
reps. The weight coaching routines on this article are whole-body exercises,
accomplished regularly and with progressively heavier weights.
Since a quantity of muscle teams are engaged in every full physique
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method to construct muscle and achieve energy. As A Substitute
of performing a set for a prescribed variety of reps, in an AMRAP set the lifter will see how many reps
they will achieve whereas still sustaining correct type.
This lets the lifters get some additional training quantity in if they’re feeling recent or get a bit much less
volume if they’re feeling drained or run down. Whether you choose
the single-leg or traditional deadlift, utilizing dumbbells or barbells, this versatile exercise engages the hamstrings, glutes and again muscles.
Type is critical on this train, so be sure to maintain a flat again and slight bend in your knees.
If you’re feeling your again rounding, scale back the
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So now, let’s take a look at a few of the components to consider when creating a teen’s training plan. This provides
you with the skillset to start to learn to build your individual routine (after following the above program for 6 months,
of course). This means coaching good, which includes
knowing the ideal training variables for teenagers, tips on how to train for
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alike). Luckily, you’ve come to the proper place, as a outcome of we’re about to get into all of that.
A few of the exercises in this routine are nice substitutes for
the ones rarely seen exterior the fitness center.
And should you don’t have a seated calf elevate
machine lying around the lounge, we’ve got you covered
with the dumbbell version. There are more «rest days» each week than exercise days so
it’s possible to make amends for one missed
session.
A place for for many who believe that correct food plan and intense coaching are all you should
build an incredible physique. Talk About NANBF/IPE, INBF/WNBF, OCB, ABA,
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for the pure lifters, train routines and more! All are welcome right here
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Some will choose to train triceps with chest,
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You may find that legs respond finest to
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However whenever you follow full body coaching you shift emphasis from muscle to muscle which lets
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GZCLP is a strength program developed for novice lifters to be
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The push press sits somewhere between the strict overhead press and the jerk.
The program balances skill growth with energy work for regular improvement without overwhelming volume.
Whether you’re new to the sport or getting again after a layoff or lengthy hiatus and wish to refine your fundamentals, this program will set you up
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