Chelating anticoagulants reduce plasma doxycycline measurements: implications for doxy PEP monitoring

Doxycycline post-exposure prophylaxis is recommended for men who have sex with men at high risk for sexually transmitted infections. Accurate doxycycline measures ensure consistent evaluation of adherence and efficacy. Participants received 200 mg doxycycline (blood collected in citrate [n = 20] or heparin [n = 14] tubes). Ex vivo analyses compared exogenous doxycycline spiked into blood from matched donors collected in citrate and heparin (n = 8) or EDTA and heparin (n = 9). Plasma doxycycline was quantified with liquid chromatography-tandem mass spectrometry and reported as geometric mean [95% CI]. After dosing, plasma doxycycline AUC24–72 h from citrate blood (17.07 µg/mL*hr [13.89–20.99]) was 3-times lower than heparin blood (54.57 [44.18–67.40]). Similarly, reduced plasma doxycycline was observed when drug was spiked into citrate (0.062 µg/mL [0.059–0.065]) versus heparin blood (0.084 µg/mL [0.077–0.092]) from matched donors (p = 0.0002). EDTA blood, also showed significantly lower plasma doxycycline (0.052 µg/mL [0.049–0.054]) than heparin blood (0.078 µg/mL [0.071–0.084]) (p < 0.0001). Chelating anticoagulants significantly reduce plasma doxycycline concentrations, likely through disruption of doxycycline–metal ion complexes and increased drug partitioning in red blood cells. Pharmacologically focused doxycycline research should prioritize blood collection in non-chelating anticoagulants or apply a correction factor if chelating anticoagulants are used. NCT04860505, NCT05853120, and NCT06545656.