Background:
Clinical trials of Doxy-PEP demonstrated high efficacy in preventing bacterial sexually transmitted infections (STIs) among men who have sex with men but not in women. Low Doxy-PEP efficacy observed among women may be related to poor adherence highlighting the importance of objective adherence monitoring in future trials and implementation studies. We examined doxycycline (DOXY) concentrations in urine and plasma, two specimen types commonly collected for STI testing, following a single oral DOXY dose to identify objective adherence markers of Doxy-PEP dosing.
Methods:
Eleven male and 9 female participants provided blood and urine up to 7 days after receiving a 200 mg oral DOXY dose. DOXY was measured in plasma and urine by liquid chromatography-mass spectrometry with a lower limit of quantification of 10 ng/mL. DOXY concentrations are reported as median and interquartile range. Adherence indicators were identified as the 10th percentile concentration at each time point.
Results:
Plasma DOXY concentrations peaked 2 hours after dosing and declined to 0.487 µg/mL (0.402 – 0.682 µg/mL) 24 hours after dosing. Plasma DOXY remained measurable in all participants 96 hours after dosing (0.043 µg/mL; 0.032 – 0.067 µg/mL) but became undetectable in 13 of 16 participants by 7 days post dose. Urine DOXY concentrations were significantly greater than those in plasma with a urine to plasma ratio of 38:1 (9:1 – 103:1; p < 0.001). Urine DOXY concentrations also peaked 2 hours after dosing and declined to 13.1 µg/mL (6.8 – 28.5 µg/mL) 24 hours after dosing but remained measurable in 15 of 16 participants 7 days after dosing at 0.202 µg/mL (0.137 – 0.318 µg/mL). DOXY adherence indicators for plasma were determined to be 0.30 and 0.03 µg/mL at 1 and 4 days after dosing, respectively, while urine adherence indicators were determined to be 3.00, 0.35 and 0.07 µg/mL at 1, 4 and 7 days after dosing, respectively. Concentrations were not significantly different between male and female participants at each time point.
Conclusions:
We identified adherence measures after a single DOXY dose within a pharmacologic tail of 4 and 7 days in plasma and urine, respectively. The data will inform and enable adherence testing in clinical studies to better assess Doxy-PEP efficacy.