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Comparative Bioavailability of Oral Granule Formulations of the HIV Antiretroviral Drugs Doravirine, Lamivudine, and Tenofovir Disoproxil Fumarate
Doravirine is a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus-1 infection, available as a single tablet in combination with other antiretroviral agents or as a fixed-dose regimen with lamivudine and tenofovir disoproxil fumarate (TDF). Alt...
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Published in: | AAPS PharmSciTech 2020-02, Vol.21 (3), p.91-91, Article 91 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Doravirine is a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus-1 infection, available as a single tablet in combination with other antiretroviral agents or as a fixed-dose regimen with lamivudine and tenofovir disoproxil fumarate (TDF). Alternative formulations of these drugs are being developed for individuals who have difficulty swallowing tablets. Two phase 1 trials were conducted, both in 24 healthy adults, to assess the pharmacokinetics of uncoated and coated oral granule formulations of doravirine, lamivudine, and TDF administered alone and with vanilla pudding or apple sauce. The pharmacokinetics for all uncoated granules, and of coated lamivudine and TDF granules, were similar to those of currently marketed tablets (geometric mean ratios [GMRs] 0.92–1.04). Coated doravirine granules had decreased AUC
0–∞
(11%) and C
max
(23%) values
versus
the tablet. The pharmacokinetics were similar for uncoated and coated doravirine granules administered with or without pudding (GMRs 0.96–1.10); administration with apple sauce increased doravirine AUC
0–∞
(26–29%), C
max
(56–59%), and C
24
(20–21%)
versus
administration of granules alone. Lamivudine granules administered with pudding or apple sauce decreased AUC
0–∞
and C
max
(14–25%)
versus
granules alone. Tenofovir AUC
0–∞
, C
max
, and C
24
increased for TDF granules administered with pudding or apple sauce
versus
alone (11–23%). Pharmacokinetic differences when administering doravirine, lamivudine, or TDF as uncoated or coated granules
versus
tablets, or when granules were administered with (
versus
without) pudding or apple sauce, are not considered clinically meaningful, supporting further development of these granule formulations. |
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ISSN: | 1530-9932 1530-9932 |
DOI: | 10.1208/s12249-020-1630-6 |