PII-131 - PHARMACOKINETIC PARAMETER ESTIMATION OF GENTAMICIN IN AN OBESE HEMODIALYSIS PATIENT: A CASE REPORT

H. Lee¹, S. Yoon², J. Chung²; ¹Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Gyeonggi, Korea, ²Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Republic of Korea.

Background: Individual pharmacokinetic (PK) parameter estimation is crucial for optimizing drug therapy in special populations. However, in the special population, the accurate estimation of PK parameters becomes particularly challenging, often compounded by sparse data.

Methods: To estimate individual PK parameters in an obese gentamicin-received patient on hemodialysis (HD), we obtained the Empirical Bayes Estimates (EBEs) using NONMEM 7.4.4. A one-compartment PK model with first-order elimination, log-normal between-subject variability for nonhemodialysis clearance (CLNHD) and volume of distribution (Vd), and a combined error model served as prior information. The model contained HD as a covariate for clearance during hemodialysis (CLHD), and creatinine clearance (CrCl) divided by the group mean value as a covariate for CLNHD. The population PK (popPK) parameter values (standard error %) of CLNHD, CLHD and Vd were 0.453 × CRCL/0.53 (0.9) L/h, 4.69 (0.86) L/h, and 23.5 (0.91) L, respectively.

Results: We report a case of a 53-year-old Korean woman who underwent HD and received gentamicin. The patient had a height of 158 cm, weighed 66.9 kg, and had a BMI of 26.8 kg/m² and an ideal body weight exceeding 1.25 times the total body weight. Notably, when considering the variance of popPK parameter, individual PK parameter CLNHD exhibited a substantial deviation from the popPK parameter, with value corresponding to 42% of the popPK parameter. The patient's CrCl (range, 1.87-4.14 L/h; mean, 2.63 L/h) was much higher than the previously reported group maximum value of 1.24 L/h, suggesting an inaccurate representation of renal function. Consequently, we obtained EBEs again with a model without CrCl effect on CLNHD, which resulted in patients' CLNHD being 138% of the population mean. In each run, Vd was 108% and 102% of the popPK parameters. The objective function value for each model was 2.80 and 1.04, respectively. The patient's CLNHD was greater than the popPK parameter mean value, but less than the popPK parameter value when estimated using the patient's original CrCl.

Conclusion: This report underscores the importance of individualized pharmacokinetic parameter estimation, particularly in obese HD patients, and highlights the potential impact of factors including obesity on gentamicin clearance.