Academic Journal
Evaluation of Doravirine Pharmacokinetics When Switching from Efavirenz to Doravirine in Healthy Subjects
| Title: | Evaluation of Doravirine Pharmacokinetics When Switching from Efavirenz to Doravirine in Healthy Subjects |
|---|---|
| Authors: | Yee, Ka Lai, Sanchez, Rosa I., Auger, Patrice, Liu, Rachael, Fan, Li, Triantafyllou, Ilias, Lai, Ming-Tain, Di Spirito, Mike, Iwamoto, Marian, Khalilieh, Sauzanne G. |
| Contributors: | Merck & Co., Inc. |
| Source: | Antimicrobial Agents and Chemotherapy ; volume 61, issue 2 ; ISSN 0066-4804 1098-6596 |
| Publisher Information: | American Society for Microbiology |
| Publication Year: | 2017 |
| Description: | Doravirine is a novel, potent nonnucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of patients with human immunodeficiency virus type 1 (HIV-1) infection that demonstrates a high genetic barrier to resistance and that has been well tolerated in studies to date. Doravirine is a candidate for patients switching from less-well-tolerated NNRTIs, such as efavirenz. While doravirine is a cytochrome P450 3A4 (CYP3A4) substrate, efavirenz induces CYP3A4; therefore, the pharmacokinetics of both drugs following a switch from efavirenz to doravirine were assessed. This was a 3-period, fixed-sequence, open-label study. Healthy adults were dosed with doravirine at 100 mg for 5 days once daily (QD) (period 1). Following a 7-day washout, efavirenz was administered at 600 mg QD for 14 days (period 2). Subsequently, doravirine was administered at 100 mg QD for 14 days (period 3). Blood samples were collected for pharmacokinetic analyses. Twenty healthy subjects were enrolled, and 17 completed the study. One day after efavirenz cessation, the doravirine area under the concentration-time curve from predosing to 24 h postdosing (AUC 0–24 ), maximum observed plasma concentration ( C max ), and observed plasma concentration at 24 h postdosing ( C 24 ) were reduced by 62%, 35%, and 85%, respectively, compared with the values with no efavirenz pretreatment. These decreases recovered to 32%, 14%, and 50% for AUC 0–24 , C max , and C 24 , respectively, by day 14 after efavirenz cessation. The doravirine C 24 reached projected therapeutic trough concentrations, based on in vitro efficacy, on day 2 following efavirenz cessation. Geometric mean efavirenz concentrations were 3,180 ng/ml on day 1 and 95.7 ng/ml on day 15, and efavirenz was present at therapeutic concentrations (>1,000 ng/ml) until day 4. Though doravirine exposure was transiently decreased following efavirenz treatment cessation, dose adjustment may not be necessary to maintain therapeutic concentrations of at least one drug during switching in ... |
| Document Type: | article in journal/newspaper |
| Language: | English |
| DOI: | 10.1128/aac.01757-16 |
| DOI: | 10.1128/AAC.01757-16 |
| Availability: | https://doi.org/10.1128/aac.01757-16 https://journals.asm.org/doi/pdf/10.1128/AAC.01757-16 |
| Rights: | https://journals.asm.org/non-commercial-tdm-license |
| Accession Number: | edsbas.D7843FD1 |
| Database: | BASE |
| FullText | Text: Availability: 0 CustomLinks: – Url: https://doi.org/10.1128/aac.01757-16# Name: EDS - BASE (ns324271) Category: fullText Text: View record from BASE |
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| Items | – Name: Title Label: Title Group: Ti Data: Evaluation of Doravirine Pharmacokinetics When Switching from Efavirenz to Doravirine in Healthy Subjects – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Yee%2C+Ka+Lai%22">Yee, Ka Lai</searchLink><br /><searchLink fieldCode="AR" term="%22Sanchez%2C+Rosa+I%2E%22">Sanchez, Rosa I.</searchLink><br /><searchLink fieldCode="AR" term="%22Auger%2C+Patrice%22">Auger, Patrice</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Rachael%22">Liu, Rachael</searchLink><br /><searchLink fieldCode="AR" term="%22Fan%2C+Li%22">Fan, Li</searchLink><br /><searchLink fieldCode="AR" term="%22Triantafyllou%2C+Ilias%22">Triantafyllou, Ilias</searchLink><br /><searchLink fieldCode="AR" term="%22Lai%2C+Ming-Tain%22">Lai, Ming-Tain</searchLink><br /><searchLink fieldCode="AR" term="%22Di+Spirito%2C+Mike%22">Di Spirito, Mike</searchLink><br /><searchLink fieldCode="AR" term="%22Iwamoto%2C+Marian%22">Iwamoto, Marian</searchLink><br /><searchLink fieldCode="AR" term="%22Khalilieh%2C+Sauzanne+G%2E%22">Khalilieh, Sauzanne G.</searchLink> – Name: Author Label: Contributors Group: Au Data: Merck & Co., Inc. – Name: TitleSource Label: Source Group: Src Data: Antimicrobial Agents and Chemotherapy ; volume 61, issue 2 ; ISSN 0066-4804 1098-6596 – Name: Publisher Label: Publisher Information Group: PubInfo Data: American Society for Microbiology – Name: DatePubCY Label: Publication Year Group: Date Data: 2017 – Name: Abstract Label: Description Group: Ab Data: Doravirine is a novel, potent nonnucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of patients with human immunodeficiency virus type 1 (HIV-1) infection that demonstrates a high genetic barrier to resistance and that has been well tolerated in studies to date. Doravirine is a candidate for patients switching from less-well-tolerated NNRTIs, such as efavirenz. While doravirine is a cytochrome P450 3A4 (CYP3A4) substrate, efavirenz induces CYP3A4; therefore, the pharmacokinetics of both drugs following a switch from efavirenz to doravirine were assessed. This was a 3-period, fixed-sequence, open-label study. Healthy adults were dosed with doravirine at 100 mg for 5 days once daily (QD) (period 1). Following a 7-day washout, efavirenz was administered at 600 mg QD for 14 days (period 2). Subsequently, doravirine was administered at 100 mg QD for 14 days (period 3). Blood samples were collected for pharmacokinetic analyses. Twenty healthy subjects were enrolled, and 17 completed the study. One day after efavirenz cessation, the doravirine area under the concentration-time curve from predosing to 24 h postdosing (AUC 0–24 ), maximum observed plasma concentration ( C max ), and observed plasma concentration at 24 h postdosing ( C 24 ) were reduced by 62%, 35%, and 85%, respectively, compared with the values with no efavirenz pretreatment. These decreases recovered to 32%, 14%, and 50% for AUC 0–24 , C max , and C 24 , respectively, by day 14 after efavirenz cessation. The doravirine C 24 reached projected therapeutic trough concentrations, based on in vitro efficacy, on day 2 following efavirenz cessation. Geometric mean efavirenz concentrations were 3,180 ng/ml on day 1 and 95.7 ng/ml on day 15, and efavirenz was present at therapeutic concentrations (>1,000 ng/ml) until day 4. Though doravirine exposure was transiently decreased following efavirenz treatment cessation, dose adjustment may not be necessary to maintain therapeutic concentrations of at least one drug during switching in ... – Name: TypeDocument Label: Document Type Group: TypDoc Data: article in journal/newspaper – Name: Language Label: Language Group: Lang Data: English – Name: DOI Label: DOI Group: ID Data: 10.1128/aac.01757-16 – Name: DOI Label: DOI Group: ID Data: 10.1128/AAC.01757-16 – Name: URL Label: Availability Group: URL Data: https://doi.org/10.1128/aac.01757-16<br />https://journals.asm.org/doi/pdf/10.1128/AAC.01757-16 – Name: Copyright Label: Rights Group: Cpyrght Data: https://journals.asm.org/non-commercial-tdm-license – Name: AN Label: Accession Number Group: ID Data: edsbas.D7843FD1 |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1128/aac.01757-16 Languages: – Text: English Titles: – TitleFull: Evaluation of Doravirine Pharmacokinetics When Switching from Efavirenz to Doravirine in Healthy Subjects Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Yee, Ka Lai – PersonEntity: Name: NameFull: Sanchez, Rosa I. – PersonEntity: Name: NameFull: Auger, Patrice – PersonEntity: Name: NameFull: Liu, Rachael – PersonEntity: Name: NameFull: Fan, Li – PersonEntity: Name: NameFull: Triantafyllou, Ilias – PersonEntity: Name: NameFull: Lai, Ming-Tain – PersonEntity: Name: NameFull: Di Spirito, Mike – PersonEntity: Name: NameFull: Iwamoto, Marian – PersonEntity: Name: NameFull: Khalilieh, Sauzanne G. – PersonEntity: Name: NameFull: Merck & Co., Inc. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 01 Type: published Y: 2017 Identifiers: – Type: issn-locals Value: edsbas – Type: issn-locals Value: edsbas.oa Titles: – TitleFull: Antimicrobial Agents and Chemotherapy ; volume 61, issue 2 ; ISSN 0066-4804 1098-6596 Type: main |
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