Santana, 25, missed out on Sunday’s Clássico Vovô between Botafogo and Fluminense with a muscle problem.
And he may have played his final game for the Brazilians with Ludogorets making an offer that has ‘pleased’ Botafogo.
Since joining Botafogo last year, Santana has made 59 appearances and scored 11 goals.
The midfielder arrived in a swap deal which saw Rodrigo Lindoso head the other way to Internacional.
A move to Ludogorets means Santana would play European football next season.
The 9-time Bulgarian First League champions are regulars in the Champions League qualifying round but for the past three seasons have dropped into the Europa League.