A fluorescence biosensor for therapeutic drug monitoring of vancomycin using in vivo microdialysis

Clinical vancomycin (Van) treatment is administered over a prolonged period to achieve a sustained therapeutic effect. Accurate, rapid, and continuous Van detection is an unmet medical monitoring need that can provide data-based guidance for doctors to adjust the dosage and treatment plan in real-world settings. In this study, we created a Van-specific, fluorescent biosensor that was combined with a microdialysis sampling technique to develop a rapid, simple, accurate, and sensitive detection method, which was validated for Van in vivo. A Van-specific probe was created by separately conjugating each of the two peptide chains of a dimeric derivative of the Van binding peptide L-Lys-D-Ala-D-Ala to a fluorescent dansyl chloride group. Subject-specific pharmacokinetics of Van was recorded in normal rabbits and rabbits with adenine-induced chronic renal failure (CRF), which indicated the feasibility of therapeutic drug monitoring in vivo. The area under the concentration-time curve (AUC_0-last) was 10,715 min μg mL^-1 (95% CI = 8,892 to 12,538) in the normal rabbits, and 14,822 and 19,025 min μg mL^-1 in two selected CRF rabbits. Furthermore, using pharmacokinetic dosing of Van in a rabbit study, we designed the dosage and drug administration interval to achieve a sustained therapeutic effect. The normal rabbits received three Van doses, 20, 5, and 5 mg kg^-1, administered at 0, 500, and 900 min, respectively. The CRF rabbits received two Van doses, 20 and 5 mg kg^-1, administered at 0 and 600 min, respectively. Thus, we established an effective method for the continuous monitoring of Van. This method facilitates the detection of Van in clinical treatment and provides the scientific basis for an effective approach to monitor blood drug levels during the clinical treatment of various diseases.