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This study aimed to estimate individual pharmacokinetic (PK) parameters in an obese hemodialysis (HD) patient receiving gentamicin and to assess the impact of obesity on gentamicin clearance (CL). A 53-year-old obese Korean woman underwent HD and received gentamicin. To estimate individual PK parameters, we employed the POSTHOC option using NONMEM® 7.4.4. A priori model contained HD as a covariate for CL during HD, and creatinine CL (CrCL), normalized by the group mean value from the a priori model, as a covariate for non-HD CL (CLNHD). Individual CLNHD exhibited a substantial reduction from the population CLNHD, with the value corresponding to 36% of the a priori model's population PK (popPK) parameter. The patient's CrCL exceeded the group maximum of the a priori information, suggesting inaccurate renal function representation. After adjusting CrCL to the group mean from the a priori model, the patient's CLNHD was 138% of the population's typical value. The objective function value for each run was 0.53 and -4.49, respectively. The patient's CLNHD was greater than the popPK parameter value but less than the popPK parameter value when estimated using the patient's original CrCL. Meanwhile, another software (Monolix®; version 2024R1) gave similar results. This study shows the importance of individualized PK parameter estimation, particularly in obese HD patients, and highlights the potential impact of factors including obesity on gentamicin CL. [ABSTRACT FROM AUTHOR] more...

Cytochrome P450 (CYP) 3A enzymes, the most important phase 1 drug-metabolizing enzymes, are responsible for 50% of the metabolism of clinically used drugs. CYP3A activity varies widely among individuals, which can affect the probability of adverse drug reactions and drug-drug interactions mediated by the induction or inhibition of the enzyme. Hence, it is important to be able to predict CYP3A activity in individuals to reduce the incidence of unexpected drug responses. To specifically and quickly measure CYP3A activity, we developed method based on gas chromatography interfaced with triple-quadrupole mass spectrometry for the quantification of cortisol, cortisone, 6β-hydroxycortisol, and 6β-hydroxycortisone simultaneously in urine and 4β-hydroxycholesterol in plasma. The results were calculated based on charcoal-stripped steroid-free urine and plasma control samples. The accuracy and precision were 93.18% to 110.0% and 1.96% to 5.34%, respectively. This method was then applied to measure endogenous steroids from urine and plasma samples of healthy Korean males and females. The calibration curves of all analytes showed good linearity with a correlation coefficient (r²) that ranged from 0.9953 to 0.9999. Therefore, this validated method can be used to measure endogenous biomarkers to predict CYP3A activity and might be applicable in the prediction of CYP3A-mediated drug interactions of new drug candidates. [ABSTRACT FROM AUTHOR] more...

Levofloxacin is a bactericidal broad spectrum antibiotic against Gram-positive and Gram-negative pathogens. A randomized, two-treatment, two-period, two-way crossover study was conducted to evaluate the bioequivalence of Lectacin 250 mg tablet, a generic levofloxacin, to its reference drug, Cravit 250 mg tablet. Each period was separated by a 7-day washout. Serial blood samples were collected until 24 h after dosing and plasma levofloxacin concentrations were determined using a high performance liquid chromatography. Pharmacokinetic parameters were analyzed using K-BE Test 2007 and BA calc 2007 (Ministry of Food and Drug Safety, Cheongju-si, South Korea). The peak concentration (Cmax) and the area under the plasma concentration versus time curve from 0 to the last measurable concentration (AUC0-t) for the generic and reference levofloxacin were 4.48±0.89 mg/L and 4.46± 0.95 mg/L, and 25.33±4.12 mg*h/L and 25.77±4.01 mg*h/L, respectively, leading to a geometric mean ratio (90% confidence interval) of the generic to the reference levofloxacin of 1.0060 (0.9339-1.0842) and 0.9810 (0.9476-1.0159), respectively, for Cmax and AUC0-t. Lectacin 250 mg tablet is bioequivalent to Cravit 250 mg tablet. [ABSTRACT FROM AUTHOR] more...

Vancomycin is a widely used glycopeptide antibiotic that requires therapeutic drug monitoring (TDM) owing to its narrow therapeutic window. It is primarily eliminated by renal excretion; thus, estimating the renal function of a patient is vital in the TDM of vancomycin. In patients with Duchenne muscular dystrophy (DMD), it is difficult to estimate the glomerular filtration rate using the serum creatinine level owing to the pathophysiological nature of the disease. Here, we report a case of a patient in whom TDM of vancomycin was performed, and explore the appropriate methods for evaluating renal function in patients with DMD based on serum levels of creatinine and cystatin C. [ABSTRACT FROM AUTHOR] more...