A drug-drug interaction study between adefovir dipivoxil and lamivudine, acetaminophen, ibuprofen and trimethoprim/sulfamethoxazole

Kearney, Brian P.; Knight, W B; Currie, Graeme; Contreras, Jennifer O.; Wolf, John E.; Gill, Stan; Fry, John; Brosgart, Carol

doi:10.1016/s0168-8278(02)80353-1

Cited by 4 publications

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“…13,14,16,17 This observation may be the result of the high capacity of the hOAT1 transport system in vivo to remove organic acids relative to circulating concentrations of exogenous substrates. This premise is further supported by the results from drug-drug interaction studies that found no renally mediated inter- actions between adefovir dipivoxil with lamivudine, acetaminophen, or ibuprofen, 18 agents that can interact with the transport of acyclic nucleotides by hOAT1 in vitro.…”

Section: Discussionmentioning

confidence: 73%

Systemic and Renal Pharmacokinetics of Adefovir and Tenofovir Upon Coadministration

Kearney

Ramanathan

Cheng

et al. 2005

The Journal of Clinical Pharma

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Adefovir and tenofovir are nucleotide analogs that undergo renal secretion by the human renal organic anion transporter. The pharmacokinetics of tenofovir and adefovir following the administration of tenofovir disoproxil fumarate and adefovir dipivoxil alone and together were determined in 24 healthy subjects in an 8-day, open-label, fixed-sequence study. Subjects received oral doses of adefovir dipivoxil on days 1 and 8 and oral doses of tenofovir disoproxil fumarate on days 2 to 8. Pharmacokinetic sampling was performed on days 1, 7, and 8. The plasma pharmacokinetics of tenofovir and adefovir were unaltered upon coadministration. Furthermore, the renal clearances (CLrenal) of tenofovir and adefovir were unaffected by their coadministration. The plasma Cmax values of tenofovir and adefovir were 33-fold and 340-fold lower than their Km values for the human renal organic anion transporter. These results demonstrate that coadministration of tenofovir disoproxil fumarate and adefovir dipivoxil does not result in substantial changes to their individual pharmacokinetic profiles.

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Section: Discussionmentioning

confidence: 73%