Systemic and renal pharmacokinetics of adefovir and tenofovir upon coadministration.
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.
Kearney
Brian P
BP
Gilead Sciences Inc, 333 Lakeside Drive, Foster City, CA 94404, USA.
Ramanathan
Srinivasan
S
Cheng
Andrew K
AK
Ebrahimi
Ramin
R
Shah
Jaymin
J
D000225:Adenine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000068698:Tenofovir
D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine; C106812:adefovir dipivoxil