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PURPOSE: Serum digoxin concentration (SDC) monitoring may be unavailable in some healthcare settings. Predicted SDC comes into play in the efficacy and toxicity monitoring of digoxin. Renal function is the important parameter for predicting SDC. This study was conducted to compare measured and predicted SDC when using creatinine clearance (CrCl) from Cockcroft-Gault (CG) equation and estimated glomerular filtration rate (eGFR) calculated from CKD-Epidemiology Collaboration (CKD-EPI), re-expressed Modification of Diet in Renal Disease (Re-MDRD4), Thai-MDRD4, and Thai-eGFR equations in Sheiner's and Konishi's pharmacokinetic models. PATIENTS AND METHODS: In this retrospective study, patients with cardiovascular disease with a steady-state of SDC within 0.5-2.0 mcg/L were enrolled. CrCl and studied eGFR adjusted for body surface area (BSA) were used in the models to determine the predicted SDC. The discrepancies of the measured and the predicted SDC were analyzed and compared. RESULTS: One hundred and twenty-four patients ranging in age from 22 to 88 years (median 60 years, IQR 50.2, 69.2) were studied. Their serum creatinine ranged from 0.40 to 1.80 mg/dL (median 0.90 mg/dL, IQR 0.79, 1.10). The mean±SD of measured SDC was 1.12±0.34 mcg/L. In the Sheiner's model, the mean predicted SDC was calculated by using the CG and the BSA adjusted CKD-EPI equations and was not different when compared with the measured levels (1.10±0.36 mcg/L (p=0.669) and 1.08±0.42 mcg/L (p=0.374), respectively). The CG, CKD-EPI, and Re-MDRD4 equations were a better fit for patients with creatinine ≥0.9 mg/dL for prediction with minimal errors. In the Konishi's model, the predicted SDC using the CG and the studied eGFR equation was lower than the measured SDC (p<0.05). CONCLUSION: In Sheiner's model, the CG and the BSA adjusted CKD-EPI equations should be used for predicting SDC, especially in patients with serum creatinine ≥0.9 mg/dL. The other studied eGFRs underestimated SDC in both Sheiner's and Konishi's model.
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INTRODUCTION: Dolutegravir may inhibit creatinine transporters in renal tubules and elevate serum creatinine levels. We investigated the usefulness of glomerular filtration rate (GFR) measured using inulin clearance (Cin), creatinine clearance (Ccr), and estimated GFR based on both serum creatinine (eGFRcre) and serum cystatin C (eGFRcys). PATIENTS & METHODS: HIV-1-infected Japanese patients with suppressed viremia and whose antiretroviral drug was switched to dolutegravir from other drugs were included (n = 108, Study 1). We compared eGFRcre and eGFRcys at the start and after 48 weeks of dolutegravir administration. For the patients providing consent, we measured Cin and Ccr (n = 15, Study 2). We assessed biases and accuracy and compared Cin with eGFRcre, eGFRcys, and Ccr. RESULTS: There were no differences in serum cystatin C and eGFRcys between baseline and at 48 weeks. Moreover, eGFRcre was significantly less accurate (within 30% of measured GFR) than both eGFRcys and Ccr (40% accuracy compared to 93% and 93%, respectively). eGFRcys was significantly less biased than eGFRcre and Ccr (p < 0.0001, p = 0.00036, respectively). No significant difference between Cin and eGFRcys was observed. eGFRcys was significantly correlated with Cin (γ = 0.85, p < 0.0001). CONCLUSIONS: eGFRcys provided the most precise estimate and most closely approximate Cin in HIV-1-infected Japanese patients with suppressed viremia treated with dolutegravir. We demonstrated clinical benefits of inulin clearance and eGFRcys. This is the first study performing inulin clearance for HIV-1-infected individuals and to show data for eGFRcys from a large cohort following a switch to dolutegravir from other antiretroviral agents.