Pharmacokinetics of apricitabine, a novel nucleoside reverse transcriptase inhibitor, in healthy volunteers treated with trimethoprim-sulphamethoxazole.
OBJECTIVE
Apricitabine is a novel deoxycytidine analogue reverse transcriptase inhibitor under development for the treatment of human immunodeficiency virus-1 infection. This study was performed to investigate potential pharmacokinetic interactions between apricitabine and trimethoprim-sulphamethoxazole.


METHODS
Pharmacokinetic parameters were calculated for single and multiple doses of apricitabine (and its metabolite BCH-335) in the presence and absence of steady-state concentrations of trimethoprim-sulphamethoxazole in healthy volunteers.


RESULTS
Plasma concentrations and areas under the concentration-time curves of apricitabine and BCH-335 metabolite were higher when apricitabine was administered with trimethoprim-sulphamethoxazole than when apricitabine was given alone, both following single doses and during multipledosing. Apricitabine was well tolerated, both when given alone and with trimethoprim-sulphamethoxazole.


CONCLUSIONS
These results suggest that exposure to apricitabine and its metabolite BCH-335 is moderately increased during co-administration with up to 960 mg q.d.s. trimethoprim-sulphamethoxazole. The size of this interaction does not appear to be influenced by the dose of trimethoprim-sulphamethoxazole and is consistent with that seen with other cytidine analogues. Dose adjustment of apricitabine does not appear to be warranted when the drug is given with trimethoprim-sulphamethoxazole.
Shiveley
L
L
Shire Pharmaceutical Development Inc., Wayne, PA, USA.
Struthers-Semple
C
C
Cox
S
S
Sawyer
J
J
D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D013997:Time Factors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000494:pharmacology*
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; C527618:BCH-335; D003841:Deoxycytidine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; C508042:apricitabine