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| Автор |
Фармакогенетические принципы коррекции панкреатита. |
Maria_Rukosueva
Ранг: Гость
Ф.И.О.: 1
Профессия: клинический ординатор
Специальность: хирургия
Адрес: Россия,г.Красноярск, ул.Краснодарская 19-706
Всего сообщений: 7
|  Опубликовано: 28-04-2006 01:46
При написании диссертации по исследованию клинической эффективности препарата "Октреотид" для лечения идиопатической формы панкреатита, возник вопрос.
Каким образом происходит метаболизм этого препарата, в особенности есть ли работы посвященные генам метаболизирующим этот препарат.
Вопрос обусловлен тем, что исследуется "Октреотид" с точки зрения фармакогенетической медицины.
Заранее благодарна. 
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Radislav
Консультант
Ранг: Старожил
Ф.И.О.: 1
Профессия: Clinical pharmacist
Специальность: Consulting
Адрес: Israel
Всего сообщений: 546
| ! Сообщение официального консультанта форума
Опубликовано: 05-05-2006 19:37
Провожу официальные данные по метаболизму октреотида
ADME
2.3.1 Absorption
A) Bioavailability
1) Subcutaneous, injection: rapidly (Kutz et al, 1986).
2.3.2 Distribution
A) Distribution Sites
1) OTHER DISTRIBUTION SITES
a) PLASMA LIPOPROTEINS
1) Plasma binding of octreotide in blood is approximately 65%, primarily bound to lipoproteins; some binding to albumin also occurs (Prod Info Sandostatin(R), 1999ai).
B) Distribution Kinetics
1) Distribution Half-Life
a) 12 minutes (Prod Info Sandostatin(R), 1999ai).
2) Volume of Distribution
a) 13.6 L (Prod Info Sandostatin(R), 1999ai).
2.3.3 Metabolism
A) Metabolism Sites and Kinetics
1) LIVER, extensive (Kutz et al, 1986).
a) The hepatic extraction of octreotide is estimated to be between 30% and 40% in healthy volunteers (Kutz et al, 1986).
2.3.4 Excretion
A) Kidney
1) Renal Excretion (%)
a) 32% (Prod Info Sandostatin(R), 1999ai).
B) Total Body Clearance
1) 10 L/hr (Prod Info Sandostatin(R), 1999ai).
a) Clearance is decreased from 10 L/hr in normal patients to 4.5 L/hr in patients with severe renal failure (Prod Info Sandostatin(R), 1999ai).
b) A decrease in clearance of octreotide by 66% has been observed at doses of 600 mcg/day relative to 150 mcg/day doses (Prod Info Sandostatin(R), 1999ai).
2.3.5 Elimination Half-life
A) Parent Compound
1) ELIMINATION HALF-LIFE
a) 1.5 hours (Kutz et al, 1986).
2) The elimination half-life of octreotide is approximately 1.5 hours after both intravenous and subcutaneous administration. This is approximately 30 times longer than the half-life of natural somatostatin (Kutz et al, 1986).
Pharmacokinetics
After subcutaneous injection, octreotide is absorbed rapidly and completely from the injection site. Peak concentrations of 5.2 ng/mL (100 mcg dose) were reached 0.4 hours after dosing. Using a specific radioimmunoassay, intravenous and subcutaneous doses were found to be bioequivalent. Peak concentrations and area under the curve values were dose proportional after intravenous single doses up to 200 mcg and subcutaneous single doses up to 500 mcg and after subcutaneous multiple doses up to 500 mcg t.i.d. (1500 mcg/day).
In healthy volunteers the distribution of octreotide from plasma was rapid (t(alpha) ½ = 0.2 h), the volume of distribution (Vdss) was estimated to be 13.6 L, and the total body clearance ranged from 7 L/hr to 10 L/hr. In blood, the distribution into the erythrocytes was found to be negligible and about 65% was bound in the plasma in a concentration-independent manner. Binding was mainly to lipoprotein and, to a lesser extent, to albumin.
The elimination of octreotide from plasma had an apparent half-life of 1.7 to 1.9 hours compared with 1-3 minutes with the natural hormone. The duration of action of Sandostatin ® (octreotide acetate) is variable but extends up to 12 hours depending upon the type of tumor. About 32% of the dose is excreted unchanged into the urine. In an elderly population, dose adjustments may be necessary due to a significant increase in the half-life (46%) and a significant decrease in the clearance (26%) of the drug.
In patients with acromegaly, the pharmacokinetics differ somewhat from those in healthy volunteers. A mean peak concentration of 2.8 ng/mL (100 mcg dose) was reached in 0.7 hours after subcutaneous dosing. The volume of distribution (Vdss) was estimated to be 21.6 ± 8.5 L and the total body clearance was increased to 18 L/h. The mean percent of the drug bound was 41.2%. The disposition and elimination half-lives were similar to normals.
In patients with renal impairment the elimination of octreotide from plasma was prolonged and total body clearance reduced. In mild renal impairment (Cl CR 40-60 mL/min) octreotide t ½ was 2.4 hours and total body clearance was 8.8 L/hr, in moderate impairment (Cl CR 10-39 mL/min) t ½ was 3.0 hours and total body clearance 7.3 L/hr, and in severely renally impaired patients not requiring dialysis (Cl CR <10 mL/min) t ½ was 3.1 hours and total body clearance was 7.6 L/hr. In patients with severe renal failure requiring dialysis, total body clearance was reduced to about half that found in healthy subjects (from approximately 10 L/hr to 4.5 L/hr).
Patients with liver cirrhosis showed prolonged elimination of drug, with octreotide t ½ increasing to 3.7 hr and total body clearance decreasing to 5.9 L/hr, whereas patients with fatty liver disease showed t ½ increased to 3.4 hr and total body clearance of 8.2 L/hr.
 
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Гость
| Опубликовано: 05-05-2006 19:56
Выражаю вам огоромную благодарность за предоставленные мне данные.
Надеюсь при переводе получить ответ на интересующий меня вопрос.
Еще раз, огромное спасибо вам.
|
Maria_Rukosueva
Ранг: Гость
Ф.И.О.: 1
Профессия: клинический ординатор
Специальность: хирургия
Адрес: Россия,г.Красноярск, ул.Краснодарская 19-706
Всего сообщений: 7
| Опубликовано: 05-05-2006 20:01
Quote:
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2006-05-05 19:56, anonimus написал:
Выражаю Вам огромную благодарность за предоставленные мне данные.
Надеюсь при переводе получить ответ на интересующий меня вопрос.
Еще раз, огромное спасибо Вам.
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