Purpose:　Photodynamic　therapy　(PDT)　schedules　are　based　on　sensitiser　dose,　light　dose,　and　drug-light　interval.　The　aim　of　the　phase　Ι　study　was　to　choose　optimal　dose　and　drug-light　interval　for　PDT　with　photocyanine　using　pharmacokinetics　(PK)　and　pharmacodynamics　(PD).　Methods:　Twenty-eight　cancer　patients　were　enrolled.　In　trial　A,　12　patients　received　one　of　four　ascending　doses　of　photocyanine　intravenously　24 h　prior　to　180–270 J/cm2　illumination.　0.2 mg/kg　dose　was　infused　to　ten　patients　12–48 h　prior　to　120 J/cm2　illumination　in　trial　B.　In　trial　C,　0.1 mg/kg　dose　was　infused　to　six　patients　6　or　12 h　prior　to　180–270 J/cm2　illumination.　Serum　concentrations　of　photocyanine　were　measured,　and　simulations　were　performed　to　assess　the　effect　of　drug　exposure　in　tissue　on　responses.　Results:　Analysis　of　photocyanine　levels　of　patients　indicated　that　the　two-compartment　model　best　fit　the　data.　Simulations　showed　that　the　rates　of　the　drug　entering　tissues　and　leaving　tissues　were　equal　at　8–12 h　after　injection.　Patients　experienced　pain　which　was　related　to　photocyanine　serum　levels,　especially　with　serum　levels　above　2500 ng/ml.　Fewer　non-responders　were　observed　at　serum　levels　higher　than　1000 ng/ml　for　illumination　at　least　12 h　after　administration.　Conclusion:　It　is　the　first　report　of　human　trials　of　photocyanine,　and　the　results　suggested　that　patients　receive　180 J/cm2　illumination　about　20–30 min　at　serum　concentrations　of　photocyanine　between　1000　and　2500 ng/ml　at　least　10 h　after　administration.　©　2020,　Springer-Verlag　GmbH　Germany,　part　of　Springer　Nature.