drugs interaction & pharmacokinetic - associate professor ph.d. nguyen tuan dung
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Drugs Interaction & PharmacokineticTRANSCRIPT
7/21/2019 Drugs Interaction & Pharmacokinetic - Associate Professor Ph.D. Nguyen Tuan Dung
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TƯƠNG TÁC DƯỢ C ĐỘNG HỌC ( Pharmacokinetic drug interactions )
PGS.TS. Nguy ễn Tu ấ n Dũng
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Tạo phức chelat
The term chelation comes from the Greek word “chele” which means claw.
Tetracyclin Fluoquinolon
Carbidopa
Levodopa
MethyldopaLevothyroxin
7/21/2019 Drugs Interaction & Pharmacokinetic - Associate Professor Ph.D. Nguyen Tuan Dung
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PHỨC CHELATE CỦA CÁC KHÁNG SINHVỚI KIM LOẠI ĐA HÓA TRỊ
( Tetracyclin, fluoquinolon )
7/21/2019 Drugs Interaction & Pharmacokinetic - Associate Professor Ph.D. Nguyen Tuan Dung
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FLUOROQUINOLON
Trước khidùng FQ
Sau khi dùngFQ
Moxifloxacin 8 4
Ciprofloxacin 6 2Gemifloxacin 3 2Levofloxacin 2 2Norfloxacin 2 2Ofloxacin 2 2Trovafloxacin 2 2
Thời điểm dùng các thuốc có chứa chất sắt
7/21/2019 Drugs Interaction & Pharmacokinetic - Associate Professor Ph.D. Nguyen Tuan Dung
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012345
0 200 400
Time (min)
P l a s m a
L e v o d o p a
( n m o l / m
l )
ParkinsonSinemet (100/25)
levodopa & carbidopaferrous sulfate (325 mg)
Campbell NRC et al: Br J clin Pharmacol 30:599-605, 1990
FeSO4 và sự hấp thu c ủa Levodopa/Carbidopa
7/21/2019 Drugs Interaction & Pharmacokinetic - Associate Professor Ph.D. Nguyen Tuan Dung
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PHÂN BỐ THUỐC
7/21/2019 Drugs Interaction & Pharmacokinetic - Associate Professor Ph.D. Nguyen Tuan Dung
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PROTEIN(Albumin)
www
w
w
ww
w
PROTEIN(Albumin)
w
w
NSAID
NSAID
www
ww
w
Tương tác thuốc ở giai đoạn phân bố
CHUY ỂN HÓA THUỐC
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2014-12-6
CHUY ỂN HÓA THUỐC
• Levodopa• Warfarin• Statin• Ergotamin• Cafein
2014-12-6
CarbidopaFe B6
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BỆNH PARKINSON
Levodopa Carbidopa
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2014-12-6
Tác dụng phụ của levodopa
Chóng mặt,Buồn nôn, nôn,Khó ngủ,
Đau đầuNước tiểu, mồ hôi hoặc nước bọt : màu đỏ, nâu, hoặc đenBuồn ngủ đột nhiên xảy ra trong các hoạt động thường ngày
7/21/2019 Drugs Interaction & Pharmacokinetic - Associate Professor Ph.D. Nguyen Tuan Dung
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38,762 Medicare dùng warfarin, cho th ấ y kháng n ấ m azole và một s ố nhóm kháng sinhcó th ể đưa đế n xu ấ t huy ế t trong vòng 2 tu ần (American Journal of Medicine, February 2012).
NGUY CƠ XUẤT HUY Ế T KHI PHỐI HỢ P WARFARIN VỚ I KHÁNG SINH
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C Y P 1A 2
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Ofloxacin 200 mg,Ciprofloxacin 250 mgEnoxacin 400 mg(all twice daily)
Caffeine(220 to 230 mg)
single doses
Inhibition ofcaffeine metabolism
Staib AH, - Interaction between quinolones and caffeine.--Drugs. 1987;34 Suppl 1:170-4.
CIPROFLOXACIN, ENOXACIN +OFLOXACIN -
7/21/2019 Drugs Interaction & Pharmacokinetic - Associate Professor Ph.D. Nguyen Tuan Dung
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So sánh nồng độ trong huyết tương của DihydroergotaminDHE (2,5 mg) khi dùng riêng lẻ và khi kết hợp với TAO (2 g)
[Azria M. et al.J. Pharmacol, 1979]
7/21/2019 Drugs Interaction & Pharmacokinetic - Associate Professor Ph.D. Nguyen Tuan Dung
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“ Ergotism ”
Necrosis of the extremities (gangrene)
“ERGOTISM”ADRAC ( Adverse Drug Reactions
Advisory Committee ) 12/2000
Phụ nữ 47 bị đau nửa đầu (migrain)
Erythromycin
Migral2 tay chân
N4 N5
Thí dụ 1
,
Clarithromycin
Erythromycin
Troleandomycin
Azithromycin
Dirithromycin
Australian Adverse Drug Reactions Bulletin, Vol 19, No 4
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THẢI TRỪ THUỐC
Bài tiết chủ động
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Gibaldi M., Int. J. Clin. Phar macol., 3, 1970
Penicillin amoxicillin, flucloxacillin,piperacillin + tazobactam
Cephalosporin cephalexin, cefazolin, cefuroxim,cefaclor, cefotaxim, ceftazidim
Quinolon Ciprofloxacin, norfloxacin
Probenecid
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TÁI HẤP THU THỤ ĐỘNG
Ion hóa(tan / nước)
Không ion hóa(tan / dầu)
pKa thuốcpH nước tiểu
Kiềm hóa nước tiểuAcid hóa nước tiểu
Thuốc acid yếu Thuốc kiềm yếu Thuốc acid yếu Thuốc kiềm yếu
Ion hóa(tan / nước)
Ion hóa(tan / nước)
Không ion hóa(tan / dầu)
Không ion hóa(tan / dầu)
Tái hấp thu Tái hấp thuThải trừ / nước tiểu
B. Urine pH
04
8
1216
20
4 5 6 7 8
Urine pH
S a l
i c y l i c a c i d r e n a
l
c l e a r a n c e
( m l / m i n )
Renal clearance of salicylate in 11 yo child with rheumatic fever treated with an antacid. Data fromLevy G, Lampman T, Kamath BL, Garrettson LK. Decreased serum salicylate concentrations inchildren with rheumatic fever treated with antacid.N Engl J Med 293:323-325, 1975.
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