ABSTRACT
INTRODUCTION: Therapeutic drug monitoring is necessary for lithium, but clinical application of several prediction strategies is still limited because of insufficient predictive accuracy. We herein proposed a suitable model, using creatinine clearance (CLcr)-based lithium clearance (Li-CL). METHODS: Patients receiving lithium provided the following information: serum lithium and creatinine concentrations, time of blood draw, dosing regimen, concomitant medications, and demographics. Li-CL was calculated as a daily dose per trough concentration for each subject, and the mean of Li-CL/CLcr was used to estimate Li-CL for another 30 subjects. Serum lithium concentrations at the time of sampling were estimated by 1-compartment model with Li-CL, fixed distribution volume (0.79 L/kg), and absorption rate (1.5/hour) in the 30 subjects. RESULTS: One hundred thirty-one samples from 82 subjects (44 men; mean±standard deviation age: 51.4±16.0 years; body weight: 64.6±13.8 kg; serum creatinine: 0.78±0.20 mg/dL; dose of lithium: 680.2±289.1 mg/day) were used to develop the pharmacokinetic model. The mean±standard deviation (95% confidence interval) of absolute error was 0.13±0.09 (0.10-0.16) mEq/L. DISCUSSION: Serum concentrations of lithium can be predicted from oral dosage with high precision, using our prediction model.
Subject(s)
Bipolar Disorder/blood , Depression/blood , Lithium/blood , Models, Biological , Schizophrenia/blood , Adult , Aged , Aged, 80 and over , Bipolar Disorder/drug therapy , Creatinine/blood , Depression/drug therapy , Dose-Response Relationship, Drug , Drug Monitoring , Female , Humans , Lithium/therapeutic use , Male , Middle Aged , Predictive Value of Tests , Schizophrenia/drug therapy , Young AdultABSTRACT
BACKGROUND: The increased risk of new-onset diabetes with statin use, including high-potency statins, is well known. However, the effects of high-potency statins on HbA1c are unclear. A retrospective cohort study was conducted to examine the effect of high-potency statins on HbA1c in patients with or without diabetes. The study enrolled new statin users identified via the electronic healthcare database of the general hospital in Japan. METHODS: Following identification of all individuals (n = 4,672) who had been prescribed a lipid lowering drug at least once between January 1, 2010 and July 31, 2014, new statin users were selected (n = 1,136). Patients were excluded if they had been prescribed treatment with a statin within the preceding 6-month period. HbA1c levels before and during high-potency statin treatment were compared using the dependent t-test. In addition, the hazard ratio for the incidence of diabetes with high-potency statin treatment was estimated, using low-potency statins as a reference. RESULTS: In patients with diabetes (n = 153), mean HbA1c (%) levels significantly increased by 0.4 % after high-potency statin use (7.57 ± 1.58; p = 0.0002) compared to baseline (7.18 ± 1.37). Similarly, HbA1c (%) levels significantly increased from 5.78 ± 0.38 to 5.92 ± 0.45 (p < 0.0001) after high-potency statin use in patients without diabetes (n = 165). Furthermore, a trend toward an increase in HbA1c was found for all of the high-potency statins irrespective of a history of diabetes. CONCLUSIONS: The use of high-potency statins may increase HbA1c levels in patients with or without diabetes.
