trimethoprim--sulfamethoxazole-drug-combination and apricitabine

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.. 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.. 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.. 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.

Topics: Administration, Oral; Adult; Anti-HIV Agents; Anti-Infective Agents; Area Under Curve; Deoxycytidine; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination