Background and Purpose: Pharmacokinetics have traditionally been assessed using concentration measurements from methods with low temporal resolution, such as blood draws, leading to profiles being estimated from sparse or blended data. Recent advances in in vivo sensors, however, now enable the collection of hundreds of observations over a few-hours for each individual drug administration. Previous analyses of such data for the antibiotic tobramycin have identified significant (several-fold), hours-scale changes in the efficiency with which this renally cleared drug is eliminated. Here we apply similar analyses to study the pharmacokinetics of another renally cleared drug, the antibiotic vancomycin. Experimental Approach: We estimate vancomycin pharmacokinetic profiles using previously collected time-dense plasma concentration measurements within six anesthetized rats. Specifically, we fit standard one- and two-compartment models, as well as time-varying one-compartment models (in which the proportionality relating concentration to elimination rate is time-varying), to these data to investigate if the time-varying models are statistically preferred for describing individual-level vancomycin pharmacokinetics, over standard one- and two-compartment models. Key Results: One-compartment models incorporating time-varying elimination proportionalities are statistically preferred over standard one- and two- compartment models for 5 of our 6 vancomycin time courses. When the initial impact of the distribution phase is removed from these data, a reciprocally time-varying one-compartment model is preferred over the standard-one compartment model in 4 of 5 considered datasets. Conclusion and Implications: These results provide further animal-model evidence that the pharmacokinetics of renally cleared drugs can vary significantly over timescales as short as a few hours.