Details of Drug-Drug Interaction
| Drug General Information (ID: DDISFTMI7P) | |||||||||
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| Drug Name | Bosentan | Drug Info | Cobicistat | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antihypertensive Agents | Antiviral Agents | |||||||
| Structure | |||||||||
| Mechanism of Bosentan-Cobicistat Interaction (Severity Level: Major) | |||||||||
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| Transporter inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Bosentan | Cobicistat | |||||||
| Mechanism 1 | OATP1B1 substrate | OATP1B1 inhibitor | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Liver organic anion transporter 1 |
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Structure
Sequence
MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKSSIIHIERRFEISSSLVGFIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCFIMGIGGVLTALPHFFMGYYRYSKETNINSSENSTSTLSTCLINQILSLNRASPEIVGKGCLKESGSYMWIYVFMGNMLRGIGETPIVPLGLSYIDDFAKEGHSSLYLGILNAIAMIGPIIGFTLGSLFSKMYVDIGYVDLSTIRITPTDSRWVGAWWLNFLVSGLFSIISSIPFFFLPQTPNKPQKERKASLSLHVLETNDEKDQTANLTNQGKNITKNVTGFFQSFKSILTNPLYVMFVLLTLLQVSSYIGAFTYVFKYVEQQYGQPSSKANILLGVITIPIFASGMFLGGYIIKKFKLNTVGIAKFSCFTAVMSLSFYLLYFFILCENKSVAGLTMTYDGNNPVTSHRDVPLSYCNSDCNCDESQWEPVCGNNGITYISPCLAGCKSSSGNKKPIVFYNCSCLEVTGLQNRNYSAHLGECPRDDACTRKFYFFVAIQVLNLFFSALGGTSHVMLIVKIVQPELKSLALGFHSMVIRALGGILAPIYFGALIDTTCIKWSTNNCGTRGSCRTYNSTSFSRVYLGLSSMLRVSSLVLYIILIYAMKKKYQEKDINASENGSVMDEANLESLNKNKHFVPSAGADSETHC
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| Gene Name | OATP1B1 | ||||||||
| Uniprot ID | SO1B1_HUMAN | ||||||||
| KEGG Pathway | hsa:10599 | ||||||||
| Protein Family | Organo anion transporter (TC 2.A.60) family | ||||||||
| Protein Function |
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
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| Mechanism Description |
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| Mechanism 2 | OATP1B3 substrate | OATP1B3 inhibitor | |||||||
| Key Mechanism Factor 2 | |||||||||
| Factor Name | Liver organic anion transporter 2 |
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Structure
Sequence
MDQHQHLNKTAESASSEKKKTRRCNGFKMFLAALSFSYIAKALGGIIMKISITQIERRFDISSSLAGLIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCLLMGTGSILTSLPHFFMGYYRYSKETHINPSENSTSSLSTCLINQTLSFNGTSPEIVEKDCVKESGSHMWIYVFMGNMLRGIGETPIVPLGISYIDDFAKEGHSSLYLGSLNAIGMIGPVIGFALGSLFAKMYVDIGYVDLSTIRITPKDSRWVGAWWLGFLVSGLFSIISSIPFFFLPKNPNKPQKERKISLSLHVLKTNDDRNQTANLTNQGKNVTKNVTGFFQSLKSILTNPLYVIFLLLTLLQVSSFIGSFTYVFKYMEQQYGQSASHANFLLGIITIPTVATGMFLGGFIIKKFKLSLVGIAKFSFLTSMISFLFQLLYFPLICESKSVAGLTLTYDGNNSVASHVDVPLSYCNSECNCDESQWEPVCGNNGITYLSPCLAGCKSSSGIKKHTVFYNCSCVEVTGLQNRNYSAHLGECPRDNTCTRKFFIYVAIQVINSLFSATGGTTFILLTVKIVQPELKALAMGFQSMVIRTLGGILAPIYFGALIDKTCMKWSTNSCGAQGACRIYNSVFFGRVYLGLSIALRFPALVLYIVFIFAMKKKFQGKDTKASDNERKVMDEANLEFLNNGEHFVPSAGTDSKTCNLDMQDNAAAN
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| Gene Name | OATP1B3 | ||||||||
| Uniprot ID | SO1B3_HUMAN | ||||||||
| KEGG Pathway | hsa:28234 | ||||||||
| Protein Family | Organo anion transporter (TC 2.A.60) family | ||||||||
| Protein Function |
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | The dosage of bosentan should be adjusted when used in combination with cobicistat or ritonavir. In patients who have been receiving cobicistat or ritonavir for at least 10 days when bosentan is prescribed, the latter should be initiated at 62.5 mg once daily or every other day depending on individual tolerability. Conversely, in patients who have been receiving bosentan when cobicistat or ritonavir is prescribed, the manufacturers recommend that use of bosentan be discontinued for at least 36 hours prior to initiating the pharmacokinetic booster. After at least 10 days following the initiation of cobicistat or ritonavir, bosentan may be resumed at 62.5 mg once daily or every other day based upon individual tolerability. There is limited experience with abrupt discontinuation of bosentan. Although no evidence for acute rebound has been observed, gradual dose reduction (62.5 mg twice daily for 3 to 7 days) should be considered to minimize the potential for clinical deterioration. | ||||||||