Background
This study performed population pharmacokinetic (PopPK) analysis of vancomycin, vital for MRSA treatment(1), in Sudanese adults. The derived PopPK model was used for model-based dose optimization, leveraging this approach to personalize therapy.
Methods
Data were collected through a retrospective, single-center, observational cohort study at Aliaa Specialist Hospital, Khartoum, Sudan. Collected per-patient data included sex, age, serum creatinine, blood urea nitrogen, and vancomycin dosing history and serum levels. CLcr was estimated using the Bjornson method (2) since data lacked patient weight and height, precluding Cockcroft-Gault. A population PK model was developed using MonolixSuite 2020R1. Monte Carlo simulations optimized dosage regimens across five CLcr groups.
Results
We retrospectively collected 194 vancomycin plasma concentrations from 99 adults. The median (interquartile range) for age (years) and CLcr (mL/min) were 65 (50–75) and 12.7 (5.52–25.78), respectively. Vancomycin PK data were best fitted using a one-compartment model with linear elimination. The estimates of clearance and volume of distribution were 2.02 L/h and 65 L, respectively. CLcr was identified as the main covariate explaining the PK variability in vancomycin CL. CL significantly decreased with decreasing CLcr. For the five CLcr groups evaluated, a tailored vancomycin daily maintenance dose (using patients’ CLcr) ranged from 200 to 1650 mg. Overall, simulations showed that 45% (CI; 41.11–47.36%) of patients would achieve a target AUC with the suggested dosages.
Conclusion
A population PK model of vancomycin was developed using data obtained from adult Sudanese patients. Model-based dose optimization can aid clinicians in selecting initial vancomycin doses that will maximize the likelihood of a favorable treatment response.
References
- Choo EJ, Chambers HF. Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia. Infect Chemother. 2016;48(4):267-73.
- Bjornsson TD. Use of serum creatinine concentrations to determine renal function. Clin Pharmacokinet. 1979;4(3):200-22.
Table: Optimal maintenance dose based on simulations with the final model.
| CLcr Group Ranges | Optimal Maintenance Dose (mg/24 h) a | AUC24–48 (mg·h/L) b | PTA for AUC24–48 > 400 (mg·h/L) c | 400 < AUC24–48 < 600 (mg·h/L) c | PTA for AUC24–48 > 600 (mg·h/L) c | Vd Median [95% Interval] L d | CL Median [95% Interval] L/h d |
| 50 – 59 | 1650 | 491.78 [263.77-864.72] | 0.72 | 0.44 | 0.28 | 66.14 [49.83 – 87.06] | 4.28 [3.11 – 5.91 |
| 40 – 49 | 1300 | 492.39 [267.29-860.49] | 0.73 | 0.44 | 0.28 | 65.64 [49.49 – 86.25] | 3.88 [2.81 – 5.35 |
| 30 – 39 | 1000 | 503.46 [279.27-863.8] | 0.74 | 0.45 | 0.3 | 65.97 [49.77 – 87.21] | 3.42 [2.5 – 4.7 |
| 20 – 29 | 400 | 489.89 [275.18-842.12] | 0.73 | 0.46 | 0.27 | 66.07 [50.11 – 87.05] | 2.9 [2.09 – 4 |
| 10 – 19 | 200 | 455.62 [259.25-778.99] | 0.66 | 0.46 | 0.2 | 65.28 [49.7 – 86.17] | 2.22 [1.61 – 3.06 |
