허브과 약물 간의 약동학적 상호작용: 그 메커니즘과 임상적 관련성

2020

https://www.mdpi.com/2075-1729/10/7/106/htm

Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance

Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance

Table 1. Examples of clinical evidence of St John’s wort (SJW)–drug interaction mediated mainly by induction in healthy volunteers or patients *.

표 1. 주로 건강한 지원자 또는 환자에서 유도에 의해 매개되는 St John's wort(SJW)-약물 상호작용의 임상 증거의 예 *.

Dose 3 × 300 mg/day	Duration	Subject Numbe	Drug Pharmacokinetic Parameters	Protein Involved
LI160 Rex Sund Jarsin LI160 Jarsin LI160 Jarsin LI160 Jarsin LI160	10 days 12 days	13 male and 12 female 12 female 13 subjects 16 male and 4 female 10 male and 11 female 9 male	↓ AUC and Cmax of digoxin ↓ AUC and Cmax of midazolam ↓ AUC of bosentan ↓ AUC and Cmax of ambrisentan ↓ Cmax of midazolam and fexofenadine ↓ AUC and Cmax of talinolol	P-gp CYP3A4 CYP2C9/3A4 CYP3A4/5 CYP2C19 CYP3A4 and P-gpCYP3A4, P-gp
Buyers Jarsin LI160 TruNatur LI160 Kira Buyers Buyers Solaray 3 × 325 mg/day Movina Jarsin LI160 Kira Kira Willmar Schwabe Pharm Jarsin LI160 Hyperiplant	14 days	6 male and 2 female 7 male and 5 female 8 male 12 subjects * 6 male and 6 female 12 male 12 male 15 male 8 male 16 male 14 male 15 male and 6 female 14 subjects 6 male and 6 female 4 male and 7 female *	↓ AUC of indinavir ↓ AUC of midazolam ↓ AUC of simvastatin ↓ AUC of amitriptyline ↓ AUC and Cmax of imatinib ↓ AUC and Cmax of omeprazole ↓ AUC and Cmax of mephenitoin AUC and Cmax no change of repaglinide ↓ AUC and Cmax of verapamil ↓ AUC and Cmax of voriconazole ↓ AUC and Cmax of zolpidem ↓ AUC and Cmax of gliclazide ↓ AUC and Cmax of nifedipine ↓ AUC and Cmax of S-ketamine ↓ AUC of docetaxel	CYP3A4 CYP3A4 CYP2C8/3A4 CYP3A4 CYP3A5, P-gp CYP2C19 CYP2C19 CYP2C8/3A4 CYP3A4 CYP3A4/5, P-gp CYP2C19 CYP3A4 CYP-2C9 CYP3A4 CYP3A4/2B6 CYP3A
LichtwerPharma AG	18 days	2 male and 8 female *	↓ AUC and Cmax of tacrolimus	CYP3A, P-gp
Modigen 2 × 300 mg/day	21 days	20 male	no effect steady-state of metformin
Rexall Sundown Buyers -	56 days 28 days	12 female 16 female 6 male and 6 female	↓ AUC and Cmax of ethinyl estradiol/norethindrone combination ↓ AUC of ethinyl estradiol/norethindrone combination ↓6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-h) ↓1-dydroxymidazolam/midazolam serum ratios (1-h) in young and in elderly subjects	CYP3A CYP3A4 CYP2E1 CYP3A4
-	31 days	2 male and 2 female *	↓of (R,S)-methadone concentration-to-dose ratios

 

Table 2. Clinical pharmacokinetic studies of Gingko biloba–drug interaction mediated mainly by induction in healthy volunteers or patients *.

건강한 지원자 또는 환자에서 주로 유도에 의해 매개되는 은행나무-약물 상호작용의 임상 약동학 연구 *.

Herbal Extract-Dose	Duration	Subject Number	Drug Pharmacokinetic Parameters	Protein Involved
Ginkgo biloba extract 240 mg standardized to 0.12% to 0.3% hypericin	14 days	12 subjects	↓ AUC of alprazolam	CYP3A4	[77]
			no effect
			half-life of elimination
Ginkgo biloba extract 240 mg	28 days	14 subjects	↓ AUC and Cmax of midazolam	CYP3A4	[78]
EGb 761 360 mg standardized to the content of 24% Ginkgo flavone glycoside and 6% terpene lactone	28 days	10 male	↓ oral clearance ↑AUC of midazolam ↓ AUC of tolbutamide	CYP3A4 Inhibition CYP2C9	[80]
Ginkgo biloba extract mg not available	some months	1 HIV-infected *	↓ plasma concentrations of efavirenz	CYP2B6	[87]
Ginkgo biloba extract 120 mg, twice daily	12 days	7 male	voriconazole no pharmacokinetic change of	extensive (2C19*1/2C19*1) and poor (2C19*2/2C19*2) metabolizers	[85]
Ginkgo biloba extract 120 mg, twice daily	14 days	14 male	bupropion no pharmacokinetic change	CYP2B6	[88]
Ginkgo biloba extract 120 mg, twice daily	28 days	12 male	diazepam no pharmacokinetic change	CYP2C19	[86]
Ginko biloba extract 360 mg/day	14 days	10 male	↑Cmax and AUC of talinolol no effects elimination half-life	P-gp inhibition	[90]
Tavonin extract 120 mg twice daily	14 days	9 male and 9 female	↑Cmax and AUC of raltegravir	P-gp inhibition	[92]
EGb 761® 120 mg twice daily or 240 mg once daily	8 days	18: male and female	caffeine tolbutamide omeprazole dextromethorphan midazolam no pharmacokinetic changes	CYP1A2 CYP2C9 CYP2C19 CYP2D6 CYP3A	[95]
Ginexin® 80 mg twice daily	7 days	34 male	Cilostazol no pharmacokinetic changes	CYP2C19 and CYP3A	[96]
Ginkgo biloba extract 360 mg)	14 days	16 male	↓AUC(0–∞) and Cmax ↑ Vd and CL atorvastatin	CYP3A4	[97]
Ginko biloba extract 120 mg twice daily	14 days	14 subjects	↑AUC(0–∞) and Cmax simvastatin	OATP1B1, CYP3A4 and BCRP	[99]

Table 3. Clinical pharmacokinetic studies of interaction between garlic extracts and drugs mediated mainly by induction in healthy volunteers or patients *.

표 3. 건강한 지원자 또는 환자에서 주로 유도에 의해 매개되는 마늘 추출물과 약물 간의 상호 작용에 대한 임상 약동학 연구 *.

Dose	Duration
Garlic oil 500 mg three times daily	28 days	6 male and 6 female	↓6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-h) in young and in elderly subjects ↓paraxanthine/caffeine serum ratios (6-h) 1-dydroxymidazolam/midazolam serum ratios (1-h) debrisoquine urinary recovery ratios no changes	CYP2El CYP1A2 CYP3A4 CY2D6	[38] [39]
Garlic powder tablets (kwai) 3 × 600 mg tablets twice daily	14 days	9 male and 6 female	AUC, Cmax, Tmax, half-life of elimination of alprazolam urinary dextromethorphan/dextrorphan ratios activity no changes	CYP34 CYP2D6	[113]
Garlic powder caplets twice daily	19 days	4 male and 6 female	↓Cmax and AUC of saquinavir	P-gp	[114]
Garlic capsules twice daily	4 days	5 male and 5 female	not pharmacokinetics changes of ritonavir		[116]

Table 4. Clinical pharmacokinetic studies of herbal–drug interactions mediated mainly by inhibition in healthy volunteers, cancer* or HIV patients.

표 4. 건강한 지원자, 암* 또는 HIV 환자에서 주로 억제에 의해 매개되는 약초-약물 상호작용의 임상 약동학 연구.

Dose	Duration of treatment
Hydrastis Canadensis root extract [Goldenseal] 900 mg, 3 times daily (no standardization claim)	28 days	6 male and 6 female	debrisoquin and midazolam pre- and post-supplementation phenotypic ratio means	CYP2D6 and CYP3A4/5	[124]
Goldenseal 1.323 mg, 3 times daily (standardized to contain 24.1 mg isoquinoline alkaloids per capsule)	14 days	8 male and 8 female	↑ Cmax, AUC(0-∞,) elimination half-life of midazolam	CYP3A4/5	[125]
Kava-kava extract138 mg/die	28 days	6 male and 6 female	chlorzoxazone pre- and post-supplementation phenotypic ratio means		[124]
Echinacea purpurea extract from root 400 mg, 4 times dail	8 days	6 male and 6 female	↓ Dose/AUC (0-∞) ↑ Cmax and Tmax of caffeine	CYPlA2	[136]
Echinacea purpurea whole plant extract 800 mg 2 times daily	28 days	6 male and 6 female	6-h serum paraxanthine-to-caffeine concentration ratio	CYP1A2	[137]
Echinacea purpurea extract from root 400 mg, 4 times daily	8 days	6 male and 6 female	↑ AUC of tolbutamide	CYP2C9	[136]
MediHerb Premium EchinaceaTM tablets 4 times daily (mixture of Echinacea angustifolia and Echinacea purpurea)	14 days	12 male	↑apparent clearance of (S)-warfarin	CYP2C9	[138]
Echinacea purpurea extract from root 400 mg, 4 times daily	8 days	6 male and 6 female	↓ AUC(0-∞) by 23% and of t½ of midazolam, administered intravenously	CYP3A4	[136]
Echinamide® Natural Factors capsule 250 mg 2 daily	28 days	8 male and 5 female	↑ AUC of midazolam by 37% and a reduction of half-life by 45%	CYP3A4	[139]
Echinaforce® 3 times daily	14 days	9 male and 2 female*	AUC(0–∞), t1/2 and Cmax of docetaxel No effect	CYP3A4	[140]
Arkocapsulas Echinacea capsule 500 mg every 6 h	14 days	14 male and 1 female°	AUC and Cmax of darunavir and ritonavir No effect	CYP3A4	[142]
Arkocapsulas Echinacea capsule 500 mg every 6 h	14 days	14 male°	AUC and Cmax of etravirine No effect	CYP3A4	[141]
Silybum marianum (milk thistle)
Silymarin (Thisilyn) 153 mg 3 times daily	21 days	12 subjects	! C8(μg/mL) of indinavir	CYP3A4	[151]
Silymarin 160 mg	14 days	7 male and 3 female	! Cmax, AUC of indinavir	CYP3A4	[152]
Milk thistle 175 mg 2 daily (standardized to 80% silymarin)	28 days	6 male and 6 female	1-hydroxymidazolam/midazolam serum ratios (1-h sample) No effect	CYP3A4	[137]
Milk thistle 300 mg 3 times daily (standardized to contain 80% silymarin)	14 days	10 male and 10 female	AUC(0-∞), Cmax and Tmax CL/F, t½ of midazolam No effect	CYP3A4	[155]
Milk thistle extract 200 mg 3 times daily (standardized to 80% silymarin)	4 or 12 days	2 male and 4 female *	No effects on irinotecan clearance	CYP3A4 UGT1Al	[156]
Silymarin (Legalon) 150 mg every 8 h	14 days	15 patients°	AUC and Cmax of darunavir and ritonavir No effect	CYP3A4	[157]
Silymarin (Legalon) 140 mg 3 times daily	14 days	12 subjects	AUC(0-12) and Cmax of midazolam, caffeine, tolbutamide, dextromethorphan No effect	CYP3A4/5, CYP1A2, CYP2C9, CYP2D6	[158]
Silymarin 420 mg/day	14 days	12 male	↑AUC(0-24), AUC(0-∞) and Cmax dose/AUC(0-∞) of losartan	CYP2C9*1/*1	[161]
Silymarin (140 mg three times daily)	14 days	18 male	↑AUC(0-36), the AUC(0-∞) and Cmax ↓oral clearance (CL/F) of talinolol	Pg-p

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